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Horizontal gene transfer

Horizontal gene transfer (HGT), sometimes referred to as lateral gene transferAny process in which a bacterium inserts genetic material into the genomes of other pathogens or into the genome of its host. Also referred to as horizontal gene transfer., is any process in which a bacterium inserts genetic material into the genomes of other pathogens or into the genome of its host. HGT represents a substantial blow to the validity of Koch's postulates, which state that any given infectious disease is caused by a single discrete and well-defined pathogen.

Increasingly, studies of genes and genomes are indicating that considerable horizontal gene transfer has occurred between bacteria.

James Lake, Molecular Biology Institute at the University of California

In fact, due to increasing evidence suggesting the importance of the phenomenon in organisms that cause disease, molecular biologists such as Peter Gogarten at the University of Connecticut have described horizontal gene transfer as “a new paradigm for biology.“

Gorgarten insists that horizontal gene transfer is “more frequent than most biologists could even imagine a decade ago” and that this reality turns the idea that we can classify organisms in a simple “tree of life” on its head.

Instead Gogarten suggests that biologists use the metaphor of a mosaic to describe the different histories combined in individual genomes and use the metaphor of a net to visualize the rich exchange of DNA among microbes.

Trading plasmids

HGT often happens via plasmids, circular molecules of DNA that can replicate independently of a pathogen’s other genetic material.

There is strong genomic evidence that bacteria often acquire evolutionary novelties from outside their ancestral population by horizontal gene transfer. Researchers at the Cancer Research Institute in Slovakia analyzed the bacterial DNA isolated from the intestinal tract of 11 American and 30 Slovak patients with HIV/AIDS. They found that the intestinal bacteria genes were more than 90% homologous to the corresponding sequence in HIV – suggesting that the bacteria and the HIV virus had traded a significant amount of genetic material.1)

The following microbes have been documented to evolve, through horizontal gene transfer, certain key evolutionary advantages:

  • Staphylococcus aureus – resistance to methicillin (an antibiotic) 2)
  • Shigella flexneri and others – resistance to multiple antibiotics 3)
  • Escherichia coli and others – iron uptake 4)
  • Proidencia rettgeri – resistance to kanamycin (an antibiotic) 5)

Acquired virulence

The transfer of DNA among pathogens means that once harmless microbes can acquire properties that allow them to cause problems for the host. “The mobile nature of… gene islands, transported between bacteria via plasmids or phages, creates the potential for acquired virulence in previously innocuous microbes,” states researcher Dave Relman of Stanford University. “This concept should inspire some reflection the next time one receives a culture report reading 'normal flora.'”6)

The bacterial pathogen Vibrio cholerae has evolved resistance to a number of antibiotics (none of which are MP antibiotics) in about 10 years' time7) passing on to other microbes what researchers have called islands of mobile pathogenecity.8) According to Beaber et al, when Vibrio cholerae is exposed to the antibiotic ciprofloxacin, it will actually promote the spread of antibiotic resistance genes.9)

Also, for example, take the bacterial species Bacillus anthracis, a species of bacteria that has two plasmids. One plasmid codes for genes that allow the pathogens to create toxins, the other codes for proteins that help it evade the immune system by living inside the white blood cells that kill and digest bacteria.

Bacillus anthracis can be found in soil, so people can pick it up relatively easily. Once inside the body it comes in contact with other species of bacteria. Let’s say it encounters Bacillus cereus, a species of bacteria that causes foodborne illness. The two bacteria may trade genetic material. If Bacillus cereus picks up the plasmids for creating toxins and evading the immune system from Bacillus anthracis, it will be much more successful at staying alive, persisting inside the cells, and ultimately causing problems for the host.

Some bacteria have more than 20 plasmids.

Also it should be noted that other types of pathogens such as viruses can and do engage in horizontal gene transfer. This activity must be accounted for. Consider this situation envisioned by biomedical researcher Trevor Marshall:

If you take the 21 plasmids of Borrelia, they can transfer DNA in 21! (21 factorial) combinations with other species, which is a VERY large number. Then you have to add in the DNA in the plasmids of the other key species - Staph, Rickettsia, Strep, Treponema, E.coli, Bacillus, and then add all of their chromosomes, add in the remaining non-plasmid bacterial species (like Mycobacteria), add the viruses, stir the soup together, accumulating new components for a few decades, and the number of combinations of pathogenic DNA in our cells becomes virtually infinite.

Trevor Marshall, PhD

Interspecies horizontal gene transfer

Horizontal gene transfer between different species of bacteria is well-documented. There is also evidence, however, that bacteria and other pathogens can transfer DNA between themselves and eukaryotic (multi-celled) organisms.

One study looked at several species of insects and roundworms infected by a parasitic bacterium called Wolbachia pipientis. The bacterium lives inside animals’ cells, including their egg cells, giving it ready access to the chromosomes that are passed on to the animals’ offspring.

When the researchers compared the genetic code of the bacterium with the code of 11 other species: four roundworms, four fruit flies, and three wasps, they found that all but three of the fruit fly species had segments of the bacterium’s genetic code embedded in their DNA.10)

Whether this occurs in humans has not yet been demonstrated, but the bacterial mutation of human DNA is consistent with the Marshall Pathogenesis and might explain the low levels of genetic concordance among people who have the same disease.

Read more

1)
Zajac V, Stevurkova V, Matelova L, Ujhazy E. Detection of HIV-1 sequences in intestinal bacteria of HIV/AIDS patients. Neuro Endocrinol Lett. 2007 Oct;28(5):591-5.
[PMID: 17984947]
2)
Ito T, Katayama Y, Hiramatsu K. Cloning and nucleotide sequence determination of the entire mec DNA of pre-methicillin-resistant Staphylococcus aureus N315. Antimicrob Agents Chemother. 1999 Jun;43(6):1449-58. doi: 10.1128/AAC.43.6.1449.
[PMID: 10348769] [PMCID: 89295] [DOI: 10.1128/AAC.43.6.1449]
3)
Boyd D, Peters GA, Cloeckaert A, Boumedine KS, Chaslus-Dancla E, Imberechts H, Mulvey MR. Complete nucleotide sequence of a 43-kilobase genomic island associated with the multidrug resistance region of Salmonella enterica serovar Typhimurium DT104 and its identification in phage type DT120 and serovar Agona. J Bacteriol. 2001 Oct;183(19):5725-32. doi: 10.1128/JB.183.19.5725-5732.2001.
[PMID: 11544236] [PMCID: 95465] [DOI: 10.1128/JB.183.19.5725-5732.2001]
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Bach S, de Almeida A, Carniel E. The Yersinia high-pathogenicity island is present in different members of the family Enterobacteriaceae. FEMS Microbiol Lett. 2000 Feb 15;183(2):289-94. doi: 10.1111/j.1574-6968.2000.tb08973.x.
[PMID: 10675599] [DOI: 10.1111/j.1574-6968.2000.tb08973.x]
5)
Böltner D, MacMahon C, Pembroke JT, Strike P, Osborn AM. R391: a conjugative integrating mosaic comprised of phage, plasmid, and transposon elements. J Bacteriol. 2002 Sep;184(18):5158-69. doi: 10.1128/JB.184.18.5158-5169.2002.
[PMID: 12193633] [PMCID: 135318] [DOI: 10.1128/JB.184.18.5158-5169.2002]
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Fredricks DN, Relman DA. Infectious agents and the etiology of chronic idiopathic diseases. Curr Clin Top Infect Dis. 1998;18:180-200.
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7) , 9)
Beaber JW, Hochhut B, Waldor MK. SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature. 2004 Jan 1;427(6969):72-4. doi: 10.1038/nature02241. Epub 2003 Dec 21.
[PMID: 14688795] [DOI: 10.1038/nature02241]
8)
Dobrindt U, Hochhut B, Hentschel U, Hacker J. Genomic islands in pathogenic and environmental microorganisms. Nat Rev Microbiol. 2004 May;2(5):414-24. doi: 10.1038/nrmicro884.
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10)
Dunning Hotopp JC, Clark ME, Oliveira DCSG, Foster JM, Fischer P, Muñoz Torres MC, Giebel JD, Kumar N, Ishmael N, Wang S, Ingram J, Nene RV, Shepard J, Tomkins J, Richards S, Spiro DJ, Ghedin E, Slatko BE, Tettelin H, Werren JH. Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Science. 2007 Sep 21;317(5845):1753-6. doi: 10.1126/science.1142490. Epub 2007 Aug 30.
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