By Kelly A. Reynolds, MSPH, Ph.D.

Yes, bacteria and viruses have sex…of sorts…and they are not always too particular about who they partner with. Close contacts in the microbial world allow for the exchange of genetic information between different organisms. This mixing of genetic elements is known to routinely occur in the environment, including food, water, biofilms and the human gut—sometimes leading to deleterious effects to public health.

A changed world
In 1990, the National Institute of Health and the US Department of Energy formally began the Human Genome Project (HGP).1 The goal of the study was to identify all of the genes and sequence the three billion nucleic acid base pairs that make up human DNA. By 1995, the first whole bacterial genome was sequenced. Four years later, HGP researchers would announce the complete sequence of the first human chromosome: chromosome 22. With consumer markets driving increased genetic research applications, tools and technologies were rapidly developed, enabling completion of the HGP years ahead of schedule. By 2006, all of the human genome was sequenced.

Throughout the course of the HGP, opportunities increased for researchers around the world to use newly available genetic methods to characterize and even create new genomes, especially with easily modified microbes. Such efforts are improving medical diagnostics and treatment, the understanding of genetic pathways of disease and evolution, and discovery of how to manipulate microbial genomes to aid in pollution mitigation, crop resilience and even fuel production. These are only a few examples of how an understanding of genomics can lead to a whole new world of applications and insights.

Manufactured benefits
Genetic engineering is the practice of inserting or deleting genes from an organism’s genome. Targeting and recombining the right genes can lead to a calculated benefit; but fears of genetically modified plants and microbes ’escaping‘ the lab or mixing with indigenous crops, have stifled the use of genetically modified organisms (GMO), also known as genetically engineered organisms (GEO).

Genetic engineering began before the HGP with the first recombinant bacteria created in 1973. E. coli, a common gut flora, was combined with genes from Salmonella. Techniques from this early experiment led to the development of a beneficial E. coli bacterial strain that could produce insulin. Nearly a decade later, bacteria were being genetically modified to protect plants from frost damage. The common soil organism, Pseudomonas, was artificially modified and became known as the ice-minus bacteria. While these harmless recombinant bacteria had the benefit of preventing the formation of ice crystals on plants, fear developed over the continued use, and possibility of these GMOs affecting rainfall by preventing the formation of ice crystals in clouds. Many more commercial applications (and controversies) would soon follow, including the creation of genetically modified zebrafish. Enter the GloFish!2 When combined with fluorescent proteins from jellyfish and coral, they glow a pretty fluorescent green, red, orange or yellow color. The fish were originally developed as indicator species that could be used to glow a different color in the presence of environmental toxins, but instead became stars of the ornamental fish trade. GloFish are the first GMO animal sold as pets in the US (GloFish are currently available everywhere, except California).

Perhaps the most widespread use of GMOs is in the production of food crops, such as corn, that are resistant to herbicides, drought and/or pests. Creating transgenic crops, microbes and animals, however, has produced controversy, primarily due to unknown effects that might be realized in nature with the introduction of ‘unnatural’ organisms.

Gene exchange in the environment
In reality, what science was perfecting with the Human Genome Project and other applications in genetic engineering, Mother Nature had already been practicing. Microbes in the environment readily exchange information, creating their own recombinant cousins, and they appear to have been doing it since the beginning of time. Exchange of genetic elements in nature occurs continuously in the environment. All bacteria appear to release some of their DNA during growth and metabolism. Likewise, they are constantly absorbing DNA from their surroundings. Viruses, known as phage, infect bacteria just like they do human cells. Researchers have shown that wherever bacteria are found, their relative viruses are also present. While viruses tend to infect the same or closely related species of bacteria, they can transfer genes from one cell to another. Anywhere bacteria are in close contact with one another, genetic information can be exchanged.3 Therefore, the genetic content of bacteria is quite fluid, allowing for changes to occur frequently. How often depends on a number of factors, including the strain’s ability to release and absorb DNA, as well as the environment itself.

Biofilms, for example, are bacteria-rich environments made up of billions of bacteria and highly diverse populations.4 While these populations are useful for wastewater treatment and pollution degradation, there has been much concern over the formation of biofilms in drinking water and POU systems. Apart from the fouling of filters, and interference with water purification processes, biofilms in drinking water are also active environments for gene swapping.5 Drinking water, including bottled and purified water, can have thousands, to tens of thousands, of harmless bacteria present. Many studies have shown that these harmless organisms harbor the same genetic elements that code for harmful effects in disease-causing bacteria (i.e., virulence factors). Harmless bacteria probably acquired these virulence factors by swapping genes with their pathogenic relatives. Scientists do not fully understand why some bacteria with the same virulence factors as harmful organisms do not also produce disease. The answer is likely in the genome and some magic combination of virulence factors, environmental conditions and host susceptibility.

When good microbes turn bad
Sometimes good bacteria turn bad. E. coli is a good example of a common gut flora of warm-blooded animals that picked up virulence factors from other organisms. Pathogenic E. coli, such as the O157:H7 or O103:H25 strains, picked up toxin-producing genes from infective viruses that carried Shiga toxin codes.6 These genes were not innate to E. coli but rather acquired from the phage. E. coli infections may result in no symptoms, mild diarrhea to severe diarrhea, kidney failure and death, depending on virulence factors.

Another recent report of good bacteria gone bad is Neisseria. Neisseria meningitides is a common cause of bacterial meningitis. Other species cause gonorrhea in humans. Some species of Neisseria, however, are harmless commensals, living on human mucous membranes without incident. Genetic analysis of the ‘good’ and ‘bad’ Neisseria species showed that there was not a clear genetic difference between the two, and that many of the commensals shared genes known to promote virulence or the ability to cause disease.7 In fact, one in 10 Neisseria were shown to take up external DNA. Where the tipping point is between friend and foe, we do not know.

Implications for the future
A 2008 article in Discovery points out 10 ways genetically engineered microbes could help humanity, including the production of cheap, effective drugs, or attack microbes with an affinity for HIV or cancerous tumors. Now that the genetic engineering genie is out of the bottle, it is unlikely that it can be put back in. With the many beneficial uses of engineered microbes and natural tendencies for intermingling, we must continue research to improve our understanding of environmental genetics. In addition, understanding how microbes recombine in nature to acquire virulence factors that lead to the emergence of new water and foodborne pathogens may help us to develop better control mechanisms for water treatment, biofilm reductions and public health protection.

References

  1. US Department of Energy Genome Programs. http://genomics.energy.gov.
  2. Yorktown Technologies. www.glofish.com.
  3. Davison, J. 1999. Genetic exchange between bacteria in the environment. Plasmid. 42: 73-91.
  4. Wuertz, S., Okabe, S. and Hausner, M. 2004. Microbial communities and their interactions in biofilm systems: an overview.
  5. Lisle, JT and Rose, JB. 1995. “Gene exchange in drinking water and bio- films by natural transformation.” Water Science and Technology. 31: 41-46.
  6. Viruses can turn harmless E. coli dangerous. April 16, 2009. www.physorg.com/news159116374.html.
  7. Stolte D. “Bad bacteria and their harmless kin share, swap genes.” 2010. UANews. http://uanews.org/printview/33150.

About the author
Dr. Kelly A. Reynolds is an Associate Professor at the University of Arizona College of Public Health. She holds a Master of Science Degree in public health (MSPH) from the University of South Florida and a doctorate in microbiology from the University of Arizona. Reynolds has been a member of the WC&P Technical Review Committee since 1997. She can be reached via email at reynolds@u.arizona.edu

 

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