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home:pathogenesis:microbiota [02.13.2019] – [Notes and comments] sallieqhome:pathogenesis:microbiota [09.14.2022] (current) – external edit 127.0.0.1
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 ====== Microbes in the human body  ====== ====== Microbes in the human body  ======
  
-According to a recent National Institutes of Health (NIH) estimate, 90% of cells in the human body are bacterial, fungal, or otherwise non-human.(({{pubmed>long:17943116}})) Although many have concluded that bacteria surely enjoy a commensal relationship with their human hosts, only a fraction of the human microbiota has been characterized, much less identified. The sheer number of non-human genes represented by the human microbiota – there are millions in our "extended genome"(({{pubmed>long:20388071}})) compared to the nearly 23,000 in the human genome – implies we have just begun to fathom the full extent to which bacteria work to facilitate their own survival.   (({{pubmed>long:28245427}}))+According to a recent National Institutes of Health (NIH) estimate, 90% of cells in the human body are bacterial, fungal, or otherwise non-human.(({{pmid>long:17943116}})) Although many have concluded that bacteria surely enjoy a commensal relationship with their human hosts, only a fraction of the human microbiota has been characterized, much less identified. The sheer number of non-human genes represented by the human microbiota – there are millions in our "extended genome"(({{pmid>long:20388071}})) compared to the nearly 23,000 in the human genome – implies we have just begun to fathom the full extent to which bacteria work to facilitate their own survival.   (({{pmid>long:28245427}}))
  
 The NIH's ongoing initiative, the Human Microbiome Project, aspires to catalog the human microbiome, also referred to as the human metagenome. Emerging insights from environmental sampling studies have shown, for example, that //in vitro// based methods for culturing bacteria have drastically underrepresented the size and diversity of bacterial populations. One environmental sample of human hands found 100 times more species than had previously been detected using purely culture-based methods. Another study which also employed high throughput genomic sequencing discovered high numbers of hydrothermal vent eubacteria on prosthetic hip joints, a species once thought only to persist in the depths of the ocean. The NIH's ongoing initiative, the Human Microbiome Project, aspires to catalog the human microbiome, also referred to as the human metagenome. Emerging insights from environmental sampling studies have shown, for example, that //in vitro// based methods for culturing bacteria have drastically underrepresented the size and diversity of bacterial populations. One environmental sample of human hands found 100 times more species than had previously been detected using purely culture-based methods. Another study which also employed high throughput genomic sequencing discovered high numbers of hydrothermal vent eubacteria on prosthetic hip joints, a species once thought only to persist in the depths of the ocean.
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-Recent research has demonstrated that the diversity, prevalence and persistence of bacteria has been consistently underestimated. Microbes form most of the world's biomass: there are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a milliliter (gram) of fresh water.(({{pubmed>long:9618454}})) Studies have found bacteria in areas previously thought to be completely sterile. A broad diversity of bacteria were found at all of the "clean rooms" where NASA spacecraft are assembled and in spite of the highly desiccated, nutrient-bare conditions within.(({{pubmed>long:17655710}})) +Recent research has demonstrated that the diversity, prevalence and persistence of bacteria has been consistently underestimated. Microbes form most of the world's biomass: there are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a milliliter (gram) of fresh water.(({{pmid>long:9618454}})) Studies have found bacteria in areas previously thought to be completely sterile. A broad diversity of bacteria were found at all of the "clean rooms" where NASA spacecraft are assembled and in spite of the highly desiccated, nutrient-bare conditions within.(({{pmid>long:17655710}})) 
  
 Bacteria are no less persistent or proliferative inside the human body.  Bacteria are no less persistent or proliferative inside the human body. 
  
-One prominent researcher [[http://news.bbc.co.uk/1/hi/health/6333137.stm|called]] human skin a "virtual zoo of bacteria."(({{pubmed>long:17293459}})) Another compared the diversity in the human gut to a rain forest.(({{pubmed>long:17014427}})) The human gut alone contains on average: 40,000 bacterial species,(({{pubmed>long:18043225}})) 9 million unique bacterial genes and 100 trillion microbial cells.(({{pubmed>long:19562079}})) According to Asher Mullard, “Between them [the bacteria in our bodies], they harbor millions of genes, compared with the paltry 20,000 estimated in the human genome. To say that you are outnumbered is a massive understatement.”(({{pubmed>long:18509412}}))+One prominent researcher [[https://news.bbc.co.uk/1/hi/health/6333137.stm|called]] human skin a "virtual zoo of bacteria."(({{pmid>long:17293459}})) Another compared the diversity in the human gut to a rain forest.(({{pmid>long:17014427}})) The human gut alone contains on average: 40,000 bacterial species,(({{pmid>long:18043225}})) 9 million unique bacterial genes and 100 trillion microbial cells.(({{pmid>long:19562079}})) According to Asher Mullard, “Between them [the bacteria in our bodies], they harbor millions of genes, compared with the paltry 20,000 estimated in the human genome. To say that you are outnumbered is a massive understatement.”(({{pmid>long:18509412}}))
  
-The global initiative known as the Human Microbiome Project currently estimates that the microorganisms that live inside or on //Homo sapiens// outnumber somatic (body) and germ cells [germ cells as in gametes, not bacteria] by a factor of ten.(({{pubmed>long:17943116}}))  To this point, only approximately 1% of this microbiota has been characterized and identified.(({{pubmed>long:17620602}})) The Human Microbiome Project aims to catalog the balance using an array of molecular sequencing techniques over the coming years.(({{pubmed>long:12037568}})) The combined genetic contributions of these microbes — in excess of 1,000,000 protein-coding genes — provide traits not encoded in our own genomes.(({{pubmed>long:12037568}})) +The global initiative known as the Human Microbiome Project currently estimates that the microorganisms that live inside or on //Homo sapiens// outnumber somatic (body) and germ cells [germ cells as in gametes, not bacteria] by a factor of ten.(({{pmid>long:17943116}}))  To this point, only approximately 1% of this microbiota has been characterized and identified.(({{pmid>long:17620602}})) The Human Microbiome Project aims to catalog the balance using an array of molecular sequencing techniques over the coming years.(({{pmid>long:12037568}})) The combined genetic contributions of these microbes — in excess of 1,000,000 protein-coding genes — provide traits not encoded in our own genomes.(({{pmid>long:12037568}})) 
  
-Since the inception of the Human Microbiome Project in 2007, dozens of research teams have gathered data which redefine what it means to be human. Some commentators have gone so far as to refer to the human body as a superorganism whose "whose metabolism represents an amalgamation of microbial and human attributes."(({{pubmed>long:16741115}})) +Since the inception of the Human Microbiome Project in 2007, dozens of research teams have gathered data which redefine what it means to be human. Some commentators have gone so far as to refer to the human body as a superorganism whose "whose metabolism represents an amalgamation of microbial and human attributes."(({{pmid>long:16741115}})) 
    
  
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 Researchers have long known that traditional methods for identifying bacteria are effective at identifying only a fraction of the bacteria in a given sample. New genomic based methods such as polymerase chain reaction (PCR) detect bacterial forms based on the presence of bacterial DNA or RNA. These new techniques are leading to some unexpected insights about bacteria. Researchers have long known that traditional methods for identifying bacteria are effective at identifying only a fraction of the bacteria in a given sample. New genomic based methods such as polymerase chain reaction (PCR) detect bacterial forms based on the presence of bacterial DNA or RNA. These new techniques are leading to some unexpected insights about bacteria.
  
-  * **Bacteria are everywhere including the world's most hostile environments** – According to [[http://www.physorg.com/news131712233.html|Penn State researcher Jennifer Loveland-Curtze]], “Microbes comprise up to one-third or more of the Earth’s biomass, yet fewer than 8,000 microbes have been described out of the approximately 3,000,000 that are presumed to exist,”  +  * **Bacteria are everywhere including the world's most hostile environments** – According to [[https://www.physorg.com/news131712233.html|Penn State researcher Jennifer Loveland-Curtze]], “Microbes comprise up to one-third or more of the Earth’s biomass, yet fewer than 8,000 microbes have been described out of the approximately 3,000,000 that are presumed to exist,”  
-    * **NASA "clean rooms"** – One would think that the the one place on Earth where bacteria do not exist is in the NASA "clean rooms" – the supposedly sterile places used to assemble aircraft. A 2007 research team compared the prevalence of bacteria found using traditional culture-based methods and ribosomal RNA gene sequence analysis. The four geographically diverse samples taken show a broad diversity in the types of bacteria able to grow in the most hostile environments including almost 100 types of bacteria, about 45 percent of which were previously unknown to science.(({{pubmed>long:17308177}})) The findings were something of a shock for NASA, an agency now forced to wonder exactly how many unknown pathogens have been taken to the moon and Mars. +    * **NASA "clean rooms"** – One would think that the the one place on Earth where bacteria do not exist is in the NASA "clean rooms" – the supposedly sterile places used to assemble aircraft. A 2007 research team compared the prevalence of bacteria found using traditional culture-based methods and ribosomal RNA gene sequence analysis. The four geographically diverse samples taken show a broad diversity in the types of bacteria able to grow in the most hostile environments including almost 100 types of bacteria, about 45 percent of which were previously unknown to science.(({{pmid>long:17308177}})) The findings were something of a shock for NASA, an agency now forced to wonder exactly how many unknown pathogens have been taken to the moon and Mars. 
-    * **Two miles below the surface of a Greenland glacier** – A Penn State team found viable "ultrasmall bacteria" in a glacial core(({{pubmed>long:16332755}})) – a habitat which is low-temperature, high-pressure, reduced-oxygen, and nutrient-poor. The core was estimated to be 120,000 years old. +    * **Two miles below the surface of a Greenland glacier** – A Penn State team found viable "ultrasmall bacteria" in a glacial core(({{pmid>long:16332755}})) – a habitat which is low-temperature, high-pressure, reduced-oxygen, and nutrient-poor. The core was estimated to be 120,000 years old. 
-    * **Deepest layer of the earth's crust** – A [[http://www.newscientist.com/article/mg20827874.800-life-is-found-in-deepest-layer-of-earths-crust.html|2010 analysis]] of the deepest layer of the Earth's oceanic crust has revealed a new ecosystem living over a kilometer beneath our feet. It is the first time that life has been found in the crust's deepest layer.(({{pubmed>long:21079766}})) +    * **Deepest layer of the earth's crust** – A [[https://www.newscientist.com/article/mg20827874.800-life-is-found-in-deepest-layer-of-earths-crust.html|2010 analysis]] of the deepest layer of the Earth's oceanic crust has revealed a new ecosystem living over a kilometer beneath our feet. It is the first time that life has been found in the crust's deepest layer.(({{pmid>long:21079766}})) 
-[{{ :home:pathogenesis:types.jpeg?|**Intrapersonal and interpersonal variability of the human microbiome is profound**. A [[http://www.ncbi.nlm.nih.gov/pubmed/20534435|2012 study]] of the human vaginal microbiome found profound shifts over time and between subjects. Red bars indicate menses.}}] +[{{ :home:pathogenesis:types.jpeg?|**Intrapersonal and interpersonal variability of the human microbiome is profound**. A [[https://www.ncbi.nlm.nih.gov/pubmed/20534435|2012 study]] of the human vaginal microbiome found profound shifts over time and between subjects. Red bars indicate menses.}}] 
-    * **[[home:pathogenesis:microbiota:detecting#existence_of_microbes_in_healthy_tissue_supposed_to_be_sterile|In tissue sites once deemed sterile]]** – The Relman Lab at Stanford used real time PCR to target conserved regions of the bacterial 16S ribosomal DNA (rDNA). They concluded that there is a substantial and "normal" population of bacterial DNA sequences in the blood of even healthy individuals.(({{pubmed>long:11326021}})) +    * **[[home:pathogenesis:microbiota:detecting#existence_of_microbes_in_healthy_tissue_supposed_to_be_sterile|In tissue sites once deemed sterile]]** – The Relman Lab at Stanford used real time PCR to target conserved regions of the bacterial 16S ribosomal DNA (rDNA). They concluded that there is a substantial and "normal" population of bacterial DNA sequences in the blood of even healthy individuals.(({{pmid>long:11326021}})) 
-  * **Antibiotic resistant strains predate human discovery of antibiotics** – In a 2011 //Nature// study ([[http://www.eurekalert.org/pub_releases/2011-08/mu-rta082511.php|press release]]), researchers carefully dug ancient 30,000 year old permafrost sediments out of the Canadian Northwest and sequenced the bacterial DNA found in it.(({{pubmed>long:21881561}})) The team concluded that antibiotic resistance genes predate our use of antibiotics and offers the first direct evidence that antibiotic resistance is an ancient, naturally occurring phenomenon widespread in the environment. This should not be surprising especially when one considers that penicillin came from a mold, tetracycline and demeclocycline from a strep mutant while Vancomycin came from //Amycolatopsis orientalis//. +  * **Antibiotic resistant strains predate human discovery of antibiotics** – In a 2011 //Nature// study ([[https://www.eurekalert.org/pub_releases/2011-08/mu-rta082511.php|press release]]), researchers carefully dug ancient 30,000 year old permafrost sediments out of the Canadian Northwest and sequenced the bacterial DNA found in it.(({{pmid>long:21881561}})) The team concluded that antibiotic resistance genes predate our use of antibiotics and offers the first direct evidence that antibiotic resistance is an ancient, naturally occurring phenomenon widespread in the environment. This should not be surprising especially when one considers that penicillin came from a mold, tetracycline and demeclocycline from a strep mutant while Vancomycin came from //Amycolatopsis orientalis//. 
-  * **Each person has a unique mix of pathogens** – A study led by Dr. Noah Fierer used a high-throughput method for PCR testing to identify the number and species of bacteria present on the hands of 51 undergraduate students leaving an exam room. Each student whose bacterial "fingerprint" – that is, their unique combination of bacteria – was sequenced, carried on average 3,200 bacteria from 150 species on their hands. Only five species were found on all the students’ hands, while any two hands – even belonging to the same person – had only 13% of their bacterial species in common.(({{pubmed>long:19004758}}))  +  * **Each person has a unique mix of pathogens** – A study led by Dr. Noah Fierer used a high-throughput method for PCR testing to identify the number and species of bacteria present on the hands of 51 undergraduate students leaving an exam room. Each student whose bacterial "fingerprint" – that is, their unique combination of bacteria – was sequenced, carried on average 3,200 bacteria from 150 species on their hands. Only five species were found on all the students’ hands, while any two hands – even belonging to the same person – had only 13% of their bacterial species in common.(({{pmid>long:19004758}}))  
-  * **Communities of people have distinctive mixes of microbes** – Two human ethnic groups based in India, which could not be distinguished on the basis of human DNA markers, could be distinguished based on their patterns of //H. pylori// variation.(({{pubmed>long:15051885}}))  +  * **Communities of people have distinctive mixes of microbes** – Two human ethnic groups based in India, which could not be distinguished on the basis of human DNA markers, could be distinguished based on their patterns of //H. pylori// variation.(({{pmid>long:15051885}}))  
-  * **Communities of microbes associated with a disease may be more diverse than controls** – asthma,(({{pubmed>long:21194740}})) bacterial vaginosis(({{pubmed>long:18487399}})) +  * **Communities of microbes associated with a disease may be more diverse than controls** – asthma,(({{pmid>long:21194740}})) bacterial vaginosis(({{pmid>long:18487399}})) 
-  * **Communities of microbes associated with a disease may be less diverse than controls** – irritable bowel syndrome,(({{pubmed>long:19606407}})) Crohn's disease,(({{pubmed>long:16188921}})) type I diabetes,(({{pubmed>long:20613793}}))AIDS(({{pubmed>long:18691828}}))   +  * **Communities of microbes associated with a disease may be less diverse than controls** – irritable bowel syndrome,(({{pmid>long:19606407}})) Crohn's disease,(({{pmid>long:16188921}})) type I diabetes,(({{pmid>long:20613793}}))AIDS(({{pmid>long:18691828}}))   
-  * **Microbial variability may be relatively unrelated to food intake** – While Dumas has shown that there are significant inter-regional differences in metabolites,(({{pubmed>long:16579598}})) work on the oral microbiome implies this may not be due to food consumption. In studying the oral microbiome, Nasidzie //et al.// took saliva samples from people in twelve diverse regions throughout the world including China, Germany, Poland, Congo, Philippines, and Louisiana.(({{pubmed>long:19251737}})) His team concluded that "while there is significantly more diversity in bacterial genera compared from different individuals than from the same individual, the diversity among individuals from the same location is nearly the same as the diversity among individuals from different locations." The relative absence of variability between people in different regions implies that those factors which are highly variable, including food intake, may play a smaller than expected role in determining what at least a person's oral microbiota is. The Human Microbiome Research consortium concluded in 2012 that much of the diversity in healthy subjects remains unexplained.(({{pubmed>long:22699609}})) +  * **Microbial variability may be relatively unrelated to food intake** – While Dumas has shown that there are significant inter-regional differences in metabolites,(({{pmid>long:16579598}})) work on the oral microbiome implies this may not be due to food consumption. In studying the oral microbiome, Nasidzie //et al.// took saliva samples from people in twelve diverse regions throughout the world including China, Germany, Poland, Congo, Philippines, and Louisiana.(({{pmid>long:19251737}})) His team concluded that "while there is significantly more diversity in bacterial genera compared from different individuals than from the same individual, the diversity among individuals from the same location is nearly the same as the diversity among individuals from different locations." The relative absence of variability between people in different regions implies that those factors which are highly variable, including food intake, may play a smaller than expected role in determining what at least a person's oral microbiota is. The Human Microbiome Research consortium concluded in 2012 that much of the diversity in healthy subjects remains unexplained.(({{pmid>long:22699609}})) 
-  * **Many bacteria cannot be cultured using traditional cultivation techniques** – Using PCR, Fierer's team found that the hands of students subjects contained 332,000 genetically distinct bacteria belonging to 4,742 different species. 45% of the species detected were considered rare. This marked a hundred-fold increase in the number of bacterial species detected in previous studies that had relied on purely culture-based methods (such as the Petri dish) to characterize the human hand microbiota.(({{pubmed>long:19004758}}))  These conclusions are supported by the aformentioned study of NASA clean rooms, which found that only 0.1 to 55% of viable cells found via PCR were able to grow on defined culture medium.(({{pubmed>long:17308177}})) +  * **Many bacteria cannot be cultured using traditional cultivation techniques** – Using PCR, Fierer's team found that the hands of student subjects contained 332,000 genetically distinct bacteria belonging to 4,742 different species. 45% of the species detected were considered rare. This marked a hundred-fold increase in the number of bacterial species detected in previous studies that had relied on purely culture-based methods (such as the Petri dish) to characterize the human hand microbiota.(({{pmid>long:19004758}}))  These conclusions are supported by the aformentioned study of NASA clean rooms, which found that only 0.1 to 55% of viable cells found via PCR were able to grow on defined culture medium.(({{pmid>long:17308177}})) 
-  * **Some microbes need very few genes to persist** – The genome of the microsporidia //Encephalitozoon cuniculi// (a pathogens which infects rabbits) is widely recognized as a model for extreme reduction and compaction. At only 2.9 Mbp, the genome encodes approximately 2,000 densely packed genes and little else. However, the nuclear genome of its sister, //Encephalitozoon intestinalis//, is even more reduced; at 2.3 Mbp, it represents a 20% reduction from an already severely compacted genome.(({{pubmed>long:20865802}})) +  * **Some microbes need very few genes to persist** – The genome of the microsporidia //Encephalitozoon cuniculi// (a pathogen which infects rabbits) is widely recognized as a model for extreme reduction and compaction. At only 2.9 Mbp, the genome encodes approximately 2,000 densely packed genes and little else. However, the nuclear genome of its sister, //Encephalitozoon intestinalis//, is even more reduced; at 2.3 Mbp, it represents a 20% reduction from an already severely compacted genome.(({{pmid>long:20865802}})) 
-  * **A number of bacteria never thought to exist in man, do, and in large numbers.** – A 2007 study, for example, found [[http://www.divediscover.whoi.edu/hottopics/bacteria.html|hydrothermal vent eubacteria]] on a prosthetic hip joint, which represents fully 6% of the bacteria sequenced and analyzed.(({{pubmed>long:17501992}})) Hydrothermal vent eubacteria otherwise grow best above 176°F (80°C). +  * **A number of bacteria never thought to exist in man, do, and in large numbers.** – A 2007 study, for example, found [[https://www.divediscover.whoi.edu/hottopics/bacteria.html|hydrothermal vent eubacteria]] on a prosthetic hip joint, which represents fully 6% of the bacteria sequenced and analyzed.(({{pmid>long:17501992}})) Hydrothermal vent eubacteria otherwise grow best above 176°F (80°C). 
-  * **At least in fruit flies, gut microbes can alter mating preferences** – In a [[http://blogs.discovermagazine.com/notrocketscience/2010/11/01/gut-bacteria-change-the-sexual-preferences-of-fruit-flies/|2010 study]], mating preference was achieved by dividing a population of //Drosophila melanogaster// and rearing one part on a molasses medium and the other on a starch medium. When the isolated populations were mixed, "molasses flies" preferred to mate with other molasses flies and "starch flies" preferred to mate with other starch flies. The mating preference appeared after only one generation and was maintained for at least 37 generations. Antibiotic treatment abolished mating preference, suggesting that the fly microbiota was responsible for the phenomenon.(({{pubmed>long:21041648}}))  +  * **At least in fruit flies, gut microbes can alter mating preferences** – In a [[https://blogs.discovermagazine.com/notrocketscience/2010/11/01/gut-bacteria-change-the-sexual-preferences-of-fruit-flies/|2010 study]], mating preference was achieved by dividing a population of //Drosophila melanogaster// and rearing one part on a molasses medium and the other on a starch medium. When the isolated populations were mixed, "molasses flies" preferred to mate with other molasses flies and "starch flies" preferred to mate with other starch flies. The mating preference appeared after only one generation and was maintained for at least 37 generations. Antibiotic treatment abolished mating preference, suggesting that the fly microbiota was responsible for the phenomenon.(({{pmid>long:21041648}}))  
-  * **Bacteria practice altruism** – In a 2010 //Nature// paper, James J. Collins and his colleagues exposed one culture of //Escherichia coli//—some strains of which colonize the human and animal gut; others of which are notorious for causing disease outbreaks—to increasing amounts of an antibiotic over time. When they periodically analyzed the levels of drug resistance in the colony, they saw something unexpected: although the entire population was thriving in the presence of the drug, only a few individual bacteria were actually resistant.  Further analysis revealed that the resistant mutants were secreting a molecule called indole that thwarts their own growth but helps the rest of the population survive by activating drug-export pumps on the bacterial cell membranes.(({{pubmed>long:20811456}}))+  * **Bacteria practice altruism** – In a 2010 //Nature// paper, James J. Collins and his colleagues exposed one culture of //Escherichia coli//—some strains of which colonize the human and animal gut; others of which are notorious for causing disease outbreaks—to increasing amounts of an antibiotic over time. When they periodically analyzed the levels of drug resistance in the colony, they saw something unexpected: although the entire population was thriving in the presence of the drug, only a few individual bacteria were actually resistant.  Further analysis revealed that the resistant mutants were secreting a molecule called indole that thwarts their own growth but helps the rest of the population survive by activating drug-export pumps on the bacterial cell membranes.(({{pmid>long:20811456}}))
 ===== Forms of bacteria ===== ===== Forms of bacteria =====
  
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 //**Ernst Almquist**, a colleague of Louis Pasteur//</blockquote> //**Ernst Almquist**, a colleague of Louis Pasteur//</blockquote>
  
-Free-floating (planktonic) bacteria may be consistent with the popular conception of bacteria in the human body, but these types of bacteria are in the minority.(({{pubmed>long:11257008}})) Bacteria are distinguished by nothing if not their diversity – diversity in form, size, and habitat. Indeed, bacteria can float in the bloodstream, but they can also live inside human cells. They can exist in communities known as biofilm. One form of bacteria that has been studied for decades and about which a lot is known is the L-form.+Free-floating (planktonic) bacteria may be consistent with the popular conception of bacteria in the human body, but these types of bacteria are in the minority.(({{pmid>long:11257008}})) Bacteria are distinguished by nothing if not their diversity – diversity in form, size, and habitat. Indeed, bacteria can float in the bloodstream, but they can also live inside human cells. They can exist in communities known as biofilm. One form of bacteria that has been studied for decades and about which a lot is known is the L-form.
  
-Bacteria regularly engage in "shape shifting" between forms. For example, //Paenibacillus dendritiformis// bacteria survive overcrowding by switching between two distinct vegetative phenotypes.(({{pubmed>long:21628502}}))+Bacteria regularly engage in "shape shifting" between forms. For example, //Paenibacillus dendritiformis// bacteria survive overcrowding by switching between two distinct vegetative phenotypes.(({{pmid>long:21628502}}))
  
 ==== L-form bacteria ==== ==== L-form bacteria ====
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 ==== Other terms for very small bacteria ==== ==== Other terms for very small bacteria ====
-  * //**Mollicutes**// - A class of bacteria distinguished by the absence of a cell wall. Emil Wirostko //et al.// found mollicute-like organisms in eyes of patients with sarcoidosis and Crohn's.(({{pubmed>long:2801045}})) In a later study, Wirostko was more specific, finding "mycoplasma-like organisms," using the term the term //Mycoplasma// to the best-known genus of //Mollicutes//.(({{pubmed>long:8140710}}))+  * //**Mollicutes**// - A class of bacteria distinguished by the absence of a cell wall. Emil Wirostko //et al.// found mollicute-like organisms in eyes of patients with sarcoidosis and Crohn's.(({{pmid>long:2801045}})) In a later study, Wirostko was more specific, finding "mycoplasma-like organisms," using the term the term //Mycoplasma// to the best-known genus of //Mollicutes//.(({{pmid>long:8140710}}))
   * **//Mycobacteria//** – A genus of //Actinobacteria// including tuberculosis and leprosy.   * **//Mycobacteria//** – A genus of //Actinobacteria// including tuberculosis and leprosy.
   * **nanobacteria** –  A proposed class of cell-walled microorganisms with a size much smaller than the generally accepted lower limit size for life (about 200 nanometers for bacteria). The existence of nanobacteria as organisms is debated. Some researchers argue that nanobacteria are actually calcifying nanoparticles.   * **nanobacteria** –  A proposed class of cell-walled microorganisms with a size much smaller than the generally accepted lower limit size for life (about 200 nanometers for bacteria). The existence of nanobacteria as organisms is debated. Some researchers argue that nanobacteria are actually calcifying nanoparticles.
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-2018 electron microscope study [[http://nautil.us/issue/66/clockwork/are-there-bacteria-in-your-brain|bacteria-in-your-brain]]+2018 electron microscope study [[https://nautil.us/issue/66/clockwork/are-there-bacteria-in-your-brain|bacteria-in-your-brain]]
 =====Successive infection and variability in disease===== =====Successive infection and variability in disease=====
 <mainarticle> [[home:pathogenesis:successive_infection|Successive infection and variability in disease]] </article> <mainarticle> [[home:pathogenesis:successive_infection|Successive infection and variability in disease]] </article>
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 ===== Reconsidering classifying bacteria as species  ===== ===== Reconsidering classifying bacteria as species  =====
  
-Traditionally, bacteria have been understood to:(({{pubmed>long:16138101}})) (({{pubmed>long:12446813}})) +Traditionally, bacteria have been understood to:(({{pmid>long:16138101}})) (({{pmid>long:12446813}})) 
-  * reproduce [[http://en.wikipedia.org/wiki/Asexual_reproduction|asexually]] +  * reproduce [[https://en.wikipedia.org/wiki/Asexual_reproduction|asexually]] 
   * not recombine their genetic material with other bacterial species   * not recombine their genetic material with other bacterial species
   * be members of a clearly defined (or definable) species   * be members of a clearly defined (or definable) species
   * for a single species, be largely clones of one another   * for a single species, be largely clones of one another
  
-Recent analyses of bacterial DNA have revealed that these assumptions are misplaced. To a much greater extent than ever anticipated, bacteria rapidly and frequently share their DNA with their fellow prokaryotes – even distantly related bacteria – through a process called [[horizontal_gene|horizontal gene transfer]].(({{pubmed>long:17255503}})) Other processes such as [[http://en.wikipedia.org/wiki/Homologous_recombination|homologous recombination]] further muddle any kind of genomic coherence.(({{pubmed>long:11544367}})) As a result the diversity and variability among bacteria are much greater than anticipated.+Recent analyses of bacterial DNA have revealed that these assumptions are misplaced. To a much greater extent than ever anticipated, bacteria rapidly and frequently share their DNA with their fellow prokaryotes – even distantly related bacteria – through a process called [[horizontal_gene|horizontal gene transfer]].(({{pmid>long:17255503}})) Other processes such as [[https://en.wikipedia.org/wiki/Homologous_recombination|homologous recombination]] further muddle any kind of genomic coherence.(({{pmid>long:11544367}})) As a result the diversity and variability among bacteria are much greater than anticipated.
  
-Given the rapid diversification in the microbial world, it has become increasingly difficult to classify bacteria with traditional approaches.(({{pubmed>long:16138101}})) (({{pubmed>long:17020593}})) When it comes to bacteria, the very definition of "species" may have to be reconsidered.(({{pubmed>long:15752428}}))+Given the rapid diversification in the microbial world, it has become increasingly difficult to classify bacteria with traditional approaches.(({{pmid>long:16138101}})) (({{pmid>long:17020593}})) When it comes to bacteria, the very definition of "species" may have to be reconsidered.(({{pmid>long:15752428}}))
  
 <blockquote> <blockquote>
 There's no single such thing as a microbial species. There's too much diversity in the range of biological collections that we might call species. Recognizing the variability between different groups, we'll probably abandon the notion of there being a single cutoff in terms of species definition.... The species concept is doomed to radical irrelevance because we don't actually need it any more. Metagenomics will come in and shift the paradigm for it.... More [novel] organisms are created through [genetic] recombination than through mutation.  There's no single such thing as a microbial species. There's too much diversity in the range of biological collections that we might call species. Recognizing the variability between different groups, we'll probably abandon the notion of there being a single cutoff in terms of species definition.... The species concept is doomed to radical irrelevance because we don't actually need it any more. Metagenomics will come in and shift the paradigm for it.... More [novel] organisms are created through [genetic] recombination than through mutation. 
  
-//**W. Ford Doolittle, PhD** [[http://rpvss.ucsd.edu:8080/ramgen/calit2/metagenomics/doolittle.rm|speaking]] at Metagenomics 2006// </blockquote>+//**W. Ford Doolittle, PhD** [[https://rpvss.ucsd.edu:8080/ramgen/calit2/metagenomics/doolittle.rm|speaking]] at Metagenomics 2006// </blockquote>
  
-For example, Hanage of Imperial College of London concluded that the classification of certain isolates of //Neisseria// was inherently "fuzzy."(({{pubmed>long:15752428}}))+For example, Hanage of Imperial College of London concluded that the classification of certain isolates of //Neisseria// was inherently "fuzzy."(({{pmid>long:15752428}}))
  
  
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 That said, there is some evidence that broad classifications of species appear more often in certain kinds of tissue: That said, there is some evidence that broad classifications of species appear more often in certain kinds of tissue:
-  * The human gut seems to consist of large numbers of Firmicutes and Bacteroidetes.(({{pubmed>long:17183309}})) +  * The human gut seems to consist of large numbers of Firmicutes and Bacteroidetes.(({{pmid>long:17183309}})) 
-  * Grice //et al// showed that there was greater diversity between different regions of the human skin in a single person than between similar skin regions of different people.(({{pubmed>long:18502944}}))+  * Grice //et al// showed that there was greater diversity between different regions of the human skin in a single person than between similar skin regions of different people.(({{pmid>long:18502944}}))
  
 ===== Study of metagenomics ===== ===== Study of metagenomics =====
  
-If species are defined by a shared gene pool, phylogenetic trees (such as the kind used to describe how Darwin's finches have common ancestors) do not satisfactorily model the relationships among bacteria – not when one organism could be a member of two or more otherwise quite distinct "species" simultaneously.(({{pubmed>long:17020593}})) One commentator suggests the relationship between bacteria is actually more like that of a web.(({{pubmed>long:16820057}}))+If species are defined by a shared gene pool, phylogenetic trees (such as the kind used to describe how Darwin's finches have common ancestors) do not satisfactorily model the relationships among bacteria – not when one organism could be a member of two or more otherwise quite distinct "species" simultaneously.(({{pmid>long:17020593}})) One commentator suggests the relationship between bacteria is actually more like that of a web.(({{pmid>long:16820057}}))
  
  
-Enter metagenomics - a field which transcends the search for individual genomes. Literally "beyond genomics"(({{pubmed>long:9818143}})), metagenomics is an approach which looks at how whole communities of bacteria develop and interact including [[.:microbiota:biofilm|biofilm bacteria]], intracellular bacteria, and [[.:microbiota:lforms|L-form bacteria]]. Metagenomics provides a way of understanding the mysterious majority of microbes, which have been historically difficult to culture and classify. It is an approach, which involves taking a sample from the environment, pooling the DNA from all the different species present, fracturing it into a mixture of relatively short fragments and then sequencing the lot. +Enter metagenomics - a field which transcends the search for individual genomes. Literally "beyond genomics"(({{pmid>long:9818143}})), metagenomics is an approach which looks at how whole communities of bacteria develop and interact including [[.:microbiota:biofilm|biofilm bacteria]], intracellular bacteria, and [[.:microbiota:lforms|L-form bacteria]]. Metagenomics provides a way of understanding the mysterious majority of microbes, which have been historically difficult to culture and classify. It is an approach, which involves taking a sample from the environment, pooling the DNA from all the different species present, fracturing it into a mixture of relatively short fragments and then sequencing the lot. 
  
 Metagenomics has begun to provide valuable insights into which communities of microbes cause disease. Given that each gene codes for a protein and that a number of proteins have harmful effects, the presence of a particular gene can and has signalled the presence of a pathogenic form of bacteria. Metagenomics has begun to provide valuable insights into which communities of microbes cause disease. Given that each gene codes for a protein and that a number of proteins have harmful effects, the presence of a particular gene can and has signalled the presence of a pathogenic form of bacteria.
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-The genomic diversity and relative importance of distinct genotypes within natural bacterial populations have remained largely unknown and may remain so for years to come.(({{pubmed>long:15731455}}))+The genomic diversity and relative importance of distinct genotypes within natural bacterial populations have remained largely unknown and may remain so for years to come.(({{pmid>long:15731455}}))
  
 The Marshall Pathogenesis makes no claims about which individual microbial species, if there are such things, are to blame for chronic disease. Besides, such a consideration is ancillary. The unique and difficult to define mix of pathogens an individual has is known as his or her [[home:pathogenesis:successive_infection#pea_soup|pea soup]] – one of the definitions of which is "a dense fog." The Marshall Pathogenesis makes no claims about which individual microbial species, if there are such things, are to blame for chronic disease. Besides, such a consideration is ancillary. The unique and difficult to define mix of pathogens an individual has is known as his or her [[home:pathogenesis:successive_infection#pea_soup|pea soup]] – one of the definitions of which is "a dense fog."
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 <mainarticle>  [[home:pathogenesis:vitamind:metabolism|Metabolism of vitamin D and the Vitamin D Receptor]]</article> <mainarticle>  [[home:pathogenesis:vitamind:metabolism|Metabolism of vitamin D and the Vitamin D Receptor]]</article>
  
-At least some of the bacteria which cause disease are intracellular. These microbes take hold progressively through a process called successive infection. Chronic forms of bacteria are able to survive and reproduce by generating substances which block and turn off the Vitamin D Receptor, a key nuclear receptor which controls the innate immune response. So logical and powerful is this survival mechanism that it seems very likely that this is the primary mode by which chronic pathogenic forms persist. It simply makes too much evolutionary sense for pathogens not to take full advantage of a receptor, which according to one recent study, transcribes hundreds of genes.(({{pubmed>long:20736230}}))+At least some of the bacteria which cause disease are intracellular. These microbes take hold progressively through a process called successive infection. Chronic forms of bacteria are able to survive and reproduce by generating substances which block and turn off the Vitamin D Receptor, a key nuclear receptor which controls the innate immune response. So logical and powerful is this survival mechanism that it seems very likely that this is the primary mode by which chronic pathogenic forms persist. It simply makes evolutionary sense for pathogens to take full advantage of a receptor, which according to one recent study, transcribes hundreds of genes.(({{pmid>long:20736230}}))
  
  
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-  * [[http://www.sciencedaily.com/releases/2009/12/091211200341.htm|Bacteria Provide New Insights Into Human Decision Making]](({{pubmed>long:20660309}})) – "What each bacterium is doing is the equivalent if each individual on earth was able receive the exact information about the rate of spread of this new virus, the exact information about the intentions, to be vaccinated or not, by each person on the planet, and in addition the exact information about the health risks of side effects or being infected," said Ben Jacob, the study's lead author. "A decision is then made in the context of this vast amount of information."+  * [[https://www.sciencedaily.com/releases/2009/12/091211200341.htm|Bacteria Provide New Insights Into Human Decision Making]](({{pmid>long:20660309}})) – "What each bacterium is doing is the equivalent if each individual on earth was able receive the exact information about the rate of spread of this new virus, the exact information about the intentions, to be vaccinated or not, by each person on the planet, and in addition the exact information about the health risks of side effects or being infected," said Ben Jacob, the study's lead author. "A decision is then made in the context of this vast amount of information."
   *    * 
-  * [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726666/?tool=pubmed|Darwin and microbiomes]] – Darwin did not mention microbes in his masterpiece, although Antoni van Leeuwenhoek had already reported their existence in the mid-seventeenth century; apparently, Darwin was not aware of this discovery. As Norman Pace commented in a recent talk, “On the Origin of Species was sterile, as it was not contaminated with bacteria.” Indeed, Darwin would have been astounded to know that some of the best evidence for natural selection resided in his own gastrointestinal tract.(({{pubmed>long:19648955}}))+  * [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726666/?tool=pubmed|Darwin and microbiomes]] – Darwin did not mention microbes in his masterpiece, although Antoni van Leeuwenhoek had already reported their existence in the mid-seventeenth century; apparently, Darwin was not aware of this discovery. As Norman Pace commented in a recent talk, “On the Origin of Species was sterile, as it was not contaminated with bacteria.” Indeed, Darwin would have been astounded to know that some of the best evidence for natural selection resided in his own gastrointestinal tract.(({{pmid>long:19648955}}))
   *    * 
-  * [[http://www.sciencedaily.com/releases/2011/01/110124111138.htm|'Social-IQ Score' for Bacteria Developed]] – discussion of a 2011 paper(({{pubmed>long:21167037}})) that developed a "Social-IQ score" for bacteria +  * [[https://www.sciencedaily.com/releases/2011/01/110124111138.htm|'Social-IQ Score' for Bacteria Developed]] – discussion of a 2011 paper(({{pmid>long:21167037}})) that developed a "Social-IQ score" for bacteria 
-  * [[http://nyti.ms/pvl9GS|Swab samples collected from dozens of restaurant playgrounds reveal the widespread presence of an array of pathogens]] +  * [[https://nyti.ms/pvl9GS|Swab samples collected from dozens of restaurant playgrounds reveal the widespread presence of an array of pathogens]] 
-  * [[http://microbeminded.com/|Exploring human microbiome research]] - Amy Proal 2015 blog MICROBE MINDED+  * [[https://microbeminded.com/|Exploring human microbiome research]] - Amy Proal 2015 blog MICROBE MINDED
   * [[https://www.youtube.com/watch?v=6My9p6munj8&t=1175s|video - How the Microbiome causes Autoimmune Dysfunction]]   * [[https://www.youtube.com/watch?v=6My9p6munj8&t=1175s|video - How the Microbiome causes Autoimmune Dysfunction]]
  
 {{tag>Pathogenesis Microbes_in_the_human_body}} {{tag>Pathogenesis Microbes_in_the_human_body}}
 +<nodisp>
 ===== Notes and comments ===== ===== Notes and comments =====
  
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 [[https://micronow.org/category/clinical-and-public-health-microbiology/|clinical-and-public-health-microbiology]] – . [[https://micronow.org/category/clinical-and-public-health-microbiology/|clinical-and-public-health-microbiology]] – .
  
-[[http://www.the-scientist.com/blog/display/57667/|Nice bacteria finish last]] – resistant bacteria help their kin survive antibiotics, but at a cost+[[https://www.the-scientist.com/blog/display/57667/|Nice bacteria finish last]] – resistant bacteria help their kin survive antibiotics, but at a cost
  
 the link https://micronow.org/cohabiting-couples-have-similar-microbiomes/ the link https://micronow.org/cohabiting-couples-have-similar-microbiomes/
 will likely not function for very long after --- // 08.22.2017// will likely not function for very long after --- // 08.22.2017//
  
-PROBLEM LINK  * [[http://www.microbeworld.org/index.php?option=com_content&view=article&id=589:mts43-rob-knight-the-microbes-that-inhabit-us&catid=37:meet-the-scientist&Itemid=155|Meet the Scientist #43 - Rob Knight: The Microbes That Inhabit Us]] – Knight studies our inner ecology: the 100 trillion microbes that grow in and on our bodies. Knight explained how hundreds of species can coexist on the palm of your hand, how bacteria manipulate your immune system and maybe even your brain, and how obesity and other health problems may come down to the wrong balance of microbes.+PROBLEM LINK  * [[https://www.microbeworld.org/index.php?option=com_content&view=article&id=589:mts43-rob-knight-the-microbes-that-inhabit-us&catid=37:meet-the-scientist&Itemid=155|Meet the Scientist #43 - Rob Knight: The Microbes That Inhabit Us]] – Knight studies our inner ecology: the 100 trillion microbes that grow in and on our bodies. Knight explained how hundreds of species can coexist on the palm of your hand, how bacteria manipulate your immune system and maybe even your brain, and how obesity and other health problems may come down to the wrong balance of microbes.
 leads to website micronow home, not Rob Knight's article leads to website micronow home, not Rob Knight's article
  
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  </blockquote>   </blockquote> 
  
-<blockquote>http://www.nature.com/news/2010/100714/full/news.2010.353.html+<blockquote>https://www.nature.com/news/2010/100714/full/news.2010.353.html
  
  
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 <blockquote>BMC Genomics. 2010 Sep 7;11:488. <blockquote>BMC Genomics. 2010 Sep 7;11:488.
-Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis.(({{pubmed>long:20819230}}))+Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis.(({{pmid>long:20819230}}))
  
 Ling Z, Kong J, Liu F, Zhu H, Chen X, Wang Y, Li L, Nelson KE, Xia Y, Xiang C. Ling Z, Kong J, Liu F, Zhu H, Chen X, Wang Y, Li L, Nelson KE, Xia Y, Xiang C.
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-<blockquote>Mycobacteria inhibition of IFN-gamma induced HLA-DR gene expression by up-regulating histone deacetylation at the promoter region in human THP-1 monocytic cells(({{pubmed>long:15843570}}))+<blockquote>Mycobacteria inhibition of IFN-gamma induced HLA-DR gene expression by up-regulating histone deacetylation at the promoter region in human THP-1 monocytic cells(({{pmid>long:15843570}}))
  
 Infection of macrophages with mycobacteria has been shown to inhibit the macrophage response to IFN-gamma. In the current study, we examined the effect of Mycobacteria avium, Mycobacteria tuberculosis, and TLR2 stimulation on IFN-gamma-induced gene expression in human PMA-differentiated THP-1 monocytic cells. Mycobacterial infection inhibited IFN-gamma-induced expression of HLA-DRalpha and HLA-DRbeta mRNA and partially inhibited CIITA expression but did not affect expression of IFN regulatory factor-1 mRNA. To determine whether inhibition of histone deacetylase (HDAC) activity could rescue HLA-DR gene expression, butyric acid and MS-275, inhibitors of HDAC activity, were added at the time of M. avium or M. tuberculosis infection or TLR2 stimulation. HDAC inhibition restored the ability of these cells to express HLA-DRalpha and HLA-DRbeta mRNA in response to IFN-gamma. Histone acetylation induced by IFN-gamma at the HLA-DRalpha promoter was repressed upon mycobacteria infection or TLR2 stimulation. HDAC gene expression was not affected by mycobacterial infection. However, mycobacterial infection or TLR2 stimulation up-regulated expression of mammalian Sin3A, a corepressor that is required for MHC class II repression by HDAC. Furthermore, we show that the mammalian Sin3A corepressor is associated with the HLA-DRalpha promoter in M. avium-infected THP-1 cells stimulated with IFN-gamma. Thus, mycobacterial infection of human THP-1 cells specifically inhibits HLA-DR gene expression by a novel pathway that involves HDAC complex formation at the HLA-DR promoter, resulting in histone deacetylation and gene silencing. Infection of macrophages with mycobacteria has been shown to inhibit the macrophage response to IFN-gamma. In the current study, we examined the effect of Mycobacteria avium, Mycobacteria tuberculosis, and TLR2 stimulation on IFN-gamma-induced gene expression in human PMA-differentiated THP-1 monocytic cells. Mycobacterial infection inhibited IFN-gamma-induced expression of HLA-DRalpha and HLA-DRbeta mRNA and partially inhibited CIITA expression but did not affect expression of IFN regulatory factor-1 mRNA. To determine whether inhibition of histone deacetylase (HDAC) activity could rescue HLA-DR gene expression, butyric acid and MS-275, inhibitors of HDAC activity, were added at the time of M. avium or M. tuberculosis infection or TLR2 stimulation. HDAC inhibition restored the ability of these cells to express HLA-DRalpha and HLA-DRbeta mRNA in response to IFN-gamma. Histone acetylation induced by IFN-gamma at the HLA-DRalpha promoter was repressed upon mycobacteria infection or TLR2 stimulation. HDAC gene expression was not affected by mycobacterial infection. However, mycobacterial infection or TLR2 stimulation up-regulated expression of mammalian Sin3A, a corepressor that is required for MHC class II repression by HDAC. Furthermore, we show that the mammalian Sin3A corepressor is associated with the HLA-DRalpha promoter in M. avium-infected THP-1 cells stimulated with IFN-gamma. Thus, mycobacterial infection of human THP-1 cells specifically inhibits HLA-DR gene expression by a novel pathway that involves HDAC complex formation at the HLA-DR promoter, resulting in histone deacetylation and gene silencing.
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-[[http://www.whale.to/y/wainwright.html|EXTREME PLEOMORPHISM AND THE BACTERIAL LIFE CYCLE: A FORGOTTEN CONTROVERSY]]+[[https://www.whale.to/y/wainwright.html|EXTREME PLEOMORPHISM AND THE BACTERIAL LIFE CYCLE: A FORGOTTEN CONTROVERSY]]
  
 <blockquote> <blockquote>
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-(({{pubmed>long:12634792}}))+(({{pmid>long:12634792}}))
  
-A total of 14,000 physical interactions obtained from the GRID database were represented with the Osprey network visualization system (see http://biodata.mshri.on.ca/grid). Each edge in the graph represents an interaction between nodes, which are coloured according to Gene Ontology (GO) functional annotation. Highly connected complexes within the data set, shown at the perimeter of the central mass, are built from nodes that share at least three interactions within other complex members. The complete graph contains 4,543 nodes of 6,000 proteins encoded by the yeast genome, 12,843 interactions and an average connectivity of 2.82 per node. The 20 highly connected complexes contain 340 genes, 1,835 connections and an average connectivity of 5.39.+A total of 14,000 physical interactions obtained from the GRID database were represented with the Osprey network visualization system (see https://biodata.mshri.on.ca/grid). Each edge in the graph represents an interaction between nodes, which are coloured according to Gene Ontology (GO) functional annotation. Highly connected complexes within the data set, shown at the perimeter of the central mass, are built from nodes that share at least three interactions within other complex members. The complete graph contains 4,543 nodes of 6,000 proteins encoded by the yeast genome, 12,843 interactions and an average connectivity of 2.82 per node. The 20 highly connected complexes contain 340 genes, 1,835 connections and an average connectivity of 5.39.
 </blockquote> </blockquote>
  
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 Well, a group at Oxford has started to hone in on one likely function: to perpetuate components of the Human Microbiome. Here is a simplified version of their hypothesis: Well, a group at Oxford has started to hone in on one likely function: to perpetuate components of the Human Microbiome. Here is a simplified version of their hypothesis:
  
-http://www.tgdaily.com/general-sciences-features/52610-all-viruses-may-be-stowaways-within-our-dna +https://www.tgdaily.com/general-sciences-features/52610-all-viruses-may-be-stowaways-within-our-dna 
  
 And the more complex concepts are in two papers at PLOS. First, a commentary: And the more complex concepts are in two papers at PLOS. First, a commentary:
  
-http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001210+https://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001210
  
 and then the actual paper: and then the actual paper:
  
-http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001191+https://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001191
  
 This is an important concept, which I have touched upon a few times, but generally felt it too complex to explain in detail. Now this paper, and the two commentaries above, can help me communicate the concept  This is an important concept, which I have touched upon a few times, but generally felt it too complex to explain in detail. Now this paper, and the two commentaries above, can help me communicate the concept 
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-http://blogs.nature.com/news/thegreatbeyond/2010/11/viruses_tk.html+https://blogs.nature.com/news/thegreatbeyond/2010/11/viruses_tk.html
  
-http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001191+https://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001191
  
 It’s time for animals - including humans - to admit that the bacteria, viruses and other microbes have won. Our bodies are home to many times more bacterial cells than animal cells and countless trillions of viruses. Ancient retroviruses make up a good size chunk of our genome. Now, scientists have discovered that most any virus can set up shop in an animal's genomes and lay dormant for millions of years. It’s time for animals - including humans - to admit that the bacteria, viruses and other microbes have won. Our bodies are home to many times more bacterial cells than animal cells and countless trillions of viruses. Ancient retroviruses make up a good size chunk of our genome. Now, scientists have discovered that most any virus can set up shop in an animal's genomes and lay dormant for millions of years.
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 </blockquote> </blockquote>
  
-<blockquote>http://dx.doi.org/10.1371/journal.pbio.1001033+<blockquote>https://dx.doi.org/10.1371/journal.pbio.1001033
  
-http://www.sciencedaily.com/releases/2011/03/110322172215.htm+https://www.sciencedaily.com/releases/2011/03/110322172215.htm
  
 Most bacteria harbor toxin–antitoxin (TA) systems, in which a bacterial toxin is rendered inactive under resting conditions by its antitoxin counterpart. Under conditions of stress, however, the antitoxin is degraded, freeing the toxin to attack its host bacterium. One such TA system, PezAT, has been difficult to study in the past because the PezT toxin is so toxic without its antitoxin counterpart that bacteria die before any useful measurements can be made. Here, we use a truncated version of PezT that kills bacteria more slowly than normal, allowing us to examine the mechanisms of how this TA system operates. We find that zeta toxins convert an essential building block of bacterial cell walls (known as UNAG) into a form that prevents normal cell wall growth, causing distortions in bacterial shape that leave the bacteria vulnerable to the hydrostatic pressure of its contents. Consequently, the bacteria burst, similar to what happens when they are treated with penicillin. These results may serve useful for designing new antibiotics. Additionally, our results support the hypothesis that activation of PezT during bacterial infections may be a method by which rapidly growing bacteria can instigate a suicide program, which would promote the release of virulence factors that facilitate spread of infections.</blockquote> Most bacteria harbor toxin–antitoxin (TA) systems, in which a bacterial toxin is rendered inactive under resting conditions by its antitoxin counterpart. Under conditions of stress, however, the antitoxin is degraded, freeing the toxin to attack its host bacterium. One such TA system, PezAT, has been difficult to study in the past because the PezT toxin is so toxic without its antitoxin counterpart that bacteria die before any useful measurements can be made. Here, we use a truncated version of PezT that kills bacteria more slowly than normal, allowing us to examine the mechanisms of how this TA system operates. We find that zeta toxins convert an essential building block of bacterial cell walls (known as UNAG) into a form that prevents normal cell wall growth, causing distortions in bacterial shape that leave the bacteria vulnerable to the hydrostatic pressure of its contents. Consequently, the bacteria burst, similar to what happens when they are treated with penicillin. These results may serve useful for designing new antibiotics. Additionally, our results support the hypothesis that activation of PezT during bacterial infections may be a method by which rapidly growing bacteria can instigate a suicide program, which would promote the release of virulence factors that facilitate spread of infections.</blockquote>
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 When all are his domain.... When all are his domain....
  
-//**C.B.H**//, [[http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-443-06839-3..00158-2&isbn=978-0-443-06839-3&type=bookPage&from=content&uniqId=266284510-2|Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases]]+//**C.B.H**//, [[https://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-443-06839-3..00158-2&isbn=978-0-443-06839-3&type=bookPage&from=content&uniqId=266284510-2|Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases]]
 </blockquote> </blockquote>
  
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 BROKEN LINKS  BROKEN LINKS 
  
-  * [[http://awesome.good.is/transparency/web/1108/deadliest-pandemics/flat.html|Deadliest outbreaks in human history]] – pretty visualization of acute infections+  * [[https://awesome.good.is/transparency/web/1108/deadliest-pandemics/flat.html|Deadliest outbreaks in human history]] – pretty visualization of acute infections
  
  
-??    * [[http://www.canadaeast.com/rss/article/1263204|Microorganisms that inhabit our bodies could trigger some diseases]] - According to Dr. Marc Ouellette, scientific director of Canadian Institutes of Health Research's Institute of Infection and Immunity, "We're starting to realize that there are many, many possibilities or linkages between our microbiome and disease that we would not have expected before, especially complex diseases. This is really an emerging field where we think there are a lot of new discoveries to make that will have a direct impact in health."+??    * [[https://www.canadaeast.com/rss/article/1263204|Microorganisms that inhabit our bodies could trigger some diseases]] - According to Dr. Marc Ouellette, scientific director of Canadian Institutes of Health Research's Institute of Infection and Immunity, "We're starting to realize that there are many, many possibilities or linkages between our microbiome and disease that we would not have expected before, especially complex diseases. This is really an emerging field where we think there are a lot of new discoveries to make that will have a direct impact in health." 
 + 
 +  * [[https://www.miller-mccune.com/science-environment/bacteria-r-us-23628/|Bacteria ‘R’ Us]] – Feature article in the popular magazine //Miller-McCune// describes how bacteria have powers to engineer the environment, to communicate and to affect human well-being. They may even think. 
 +===== References =====</nodisp>
  
-  * [[http://www.miller-mccune.com/science-environment/bacteria-r-us-23628/|Bacteria ‘R’ Us]] – Feature article in the popular magazine //Miller-McCune// describes how bacteria have powers to engineer the environment, to communicate and to affect human well-being. They may even think. 
-===== References ===== 
home/pathogenesis/microbiota.1550093666.txt.gz · Last modified: 02.13.2019 by sallieq
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