August 2001: Volume 43, Number 8
The Evolution of New Bacterial Pathogens
by Kelly A. Reynolds, MSPH, Ph.D.
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We all know that new pathogens continue to emerge, but where do they come from? How can a previously unknown organism suddenly surface and wreak havoc on public health?
A number of factors contribute to the emergence of a new pathogen. They include:
• A pathogen may be previously unrecognized, undetectable or undiagnosed but prevalent in the community for some time;
• A pathogen may have always been present but harmful only to a specific group of individuals, such as the immunocompromised;
• A pathogen may be transmitted by a new exposure route, or
• A pathogen may truly be a newly evolved genetic sequence, never before present.
It's difficult to predict where new health threats will emerge. Common ailments such as most ulcers and some cases of diabetes and heart disease have recently been linked to microbial agents. Detection methods are continually improving for better isolation and diagnosis of microbes and their associated illnesses, but efficient and reliable cultural methods have yet to be developed for some of the most common microbial health threats. Changes in lifestyles and cultures play a role in the emergence of new pathogens. For example, more children are in group, day-care environments and more people are traveling nationally and internationally, resulting in an increase in pathogen exposures and more likelihood that a pathogen can move quickly from halfway across the globe. Another example, the growing population of immunocompromised individuals (i.e., HIV positive, organ transplant, chemotherapy patients, etc.) has led to an increased awareness of microbial pathogens since persons with chronic illness or stressed immune systems are more susceptible to infections and are more likely to experience increased morbidity or mortality—illness and death. Likewise, there's the graying of the Baby Boom generation in the United States, which raises similar awareness issues.
Perhaps the most daunting cause of an emerged pathogen is due to evolution of a new microbe, with different characteristics (i.e., growth temperatures, heat stability, toxin production, resistance mechanisms, etc.) and a new combination of genetic sequences—in other words, a brand new organism.
Genetically unique microbes may evolve by a number of processes, including mutation, transduction, conjugation and transformation. In the case of mutation, microbial sequences change due to either an outside stress, i.e., exposure to ultraviolet light, or the inherent inefficiency in the nucleic acid replication process of the organism—it's genetic map. In either case, the genetic sequence of the organism is altered. Mutations commonly occur in nature; however, most have no notable effect on the organism's virulence properties.
Transduction, conjugation and transformation are all events of gene transfer where organisms exchange genetic information (see Table 1). Such events have been purposefully orchestrated to enhance positive attributes of microbes. For example, a fast-growing bacteria may be genetically combined intentionally with a slow growing organism capable of degrading toxic pollutants to produce an ideal organism for use in bioremediation practices. In nature, bacteria are constantly exchanging genetic information, typically with no notable effects.
Most of the genetic information required for a functional bacterial cell is contained in the chromosome, a group of gene sequences necessary for coding processes of metabolism and replication of the bacteria. In addition, bacteria often contain extrachromosomal genetic elements controlled by factors outside the chromosome, some of which are called plasmids—an extrachromosomal ring of DNA especially of bacteria that replicate autonomously. Typically, plasmids aren't vital for the functioning of the bacterial cell but these accessory elements can help an organism establish a certain niche in the environment, aiding in their survival. In addition, these elements are easily shared with other bacteria, providing an opportunity for the combination of a variety of virulence factors that may collectively create a newly emerging pathogen.
Genetic sequencing data indicate that the Escherichia species and Salmonella species diverged from a common ancestor about 120-to-160 million years ago, around the time of the origin of mammals.2 Shigella species are thought to have arisen from E. coli about 80 million years ago, around the origin of the primate. Non-pathogenic E. coli is considered to be a part of the normal flora of the intestinal tract of humans and other warm-blooded animals and is generally harmless. Over the course of evolutionary history, E. coli appears to have undergone mutation events and acquired virulence genes from plasmids, transposons and phage—coding for particular virulence traits and/or characteristic changes. A transposon is a transposable element especially when it contains genetic material controlling functions other than those related to its relocation. A phage is short for bacteriaphage, which is a virus that infects bacteria.
Originally it's thought that a harmless strain of E. coli was converted to an enteropathogenic (EPEC)—or intestinal—strain by the acquisition of attaching and effacing (AE) genes, capable of causing lesions on epithelial cells and diarrheal symptoms. These AE genes are dependent on a secretion system that's encoded by a chromosomal pathogenicity island, designated the LEE (for "locus for enterocyte effacement") gene.3 E. coli O157:H7 appears to have subsequently evolved from the EPEC ancestor by acquiring the LEE genes followed by toxin-producing genes and other virulence factors, to produce bloody diarrhea and potentially life-threatening illness.
In 1982, two outbreaks of severe bloody diarrhea occurred in Oregon and Michigan, associated with fast-food hamburgers. At least 47 people were affected. The causative organism appeared to be a new strain of E. coli, designated as O157:H7. Characteristic of the organism is the ability to produce a harmful toxin, similar to that of Shigella species. Following the Oregon and Michigan outbreaks, questions arose as to whether the E. coli O157:H7 strain was truly a new pathogen or a newly recognized pathogen. A 10-year retrospective review of E. coli isolates archived by the Centers for Disease Control and Prevention (CDC) showed that only one (isolated from a severely ill patient in 1975) in 3,000 was identified as E. coli O157:H7, suggesting that this was a newly emerged pathogen.
In 1987, Washington became the first state to require that infection with E. coli O157:H7 be reported. Using population-based prospective studies, it was discovered in 1988 that E. coli O157:H7 was a common cause of diarrhea in Washington, and was probably underdiagnosed due to the lack of specific microbiologic testing. The lack of glucuronidase activity—involving enzymes in the liver and spleen—resulted from a spontaneous genetic mutation and separates E. coli O157:H7 from over 95 percent of other E. coli strains by utilizing selective culture media.
Between 1982 and 1995, there were 139 reported U.S. outbreaks of E. coli O157:H7.1 Originally associated with consumption of undercooked ground beef, a 1984 outbreak in a day-care center established the person-to-person transmission route. The largest outbreak of E. coli O157:H7 in the United States—with 243 cases and 4 deaths—occurred in 1989 due to the consumption of unchlorinated drinking water in Cabool, Miss.4 Since then, numerous outbreaks have been associated with a variety of foods such as dairy products and meats, water and animal routes of transmission.
Reducing your risks
Bacteria are continually evolving, mutating and sharing genetic information. Strains are known to change within a single host, complicating efforts to determine the relationship of specific organisms over geographical distributions. While the evolution of new pathogens is a definite concern, the increased virulence of well-known pathogens is also unsettling. Recent acquisition of antibiotic resistance plasmids have complicated treatment efforts for some common pathogens. Some strains of bacteria that cause tuberculosis are resistant to the three major antibiotic treatments, meaning that an infection with one of these strains may be virtually untreatable, as was the case before the advent of antibiotics.
As with most pathogens, the best way to combat newly emerging pathogens or treatment-resistant microbes is to avoid initial exposure to these organisms. Since the exposure routes are common sources such as food, water and direct human contact, it's important to follow precautionary guidelines for safe food handling, water treatment and good personal hygiene.
Shigella and Shiga toxin-producing Escherichia coli causing bloody diarrhea in Latin America Infectious Disease Clinics of North America," 14:41-65, viii, 2000.
2. Park, S., R. W. Worobo, and R. A. Durst, "Escherichia coli O157:H7 as an emerging foodborne pathogen: a literature review," Critical Reviews in Food Science and Nutrition, 39:481-502, 1999.
3. Rosenshine, I., et al., "Regulation of virulence genes and host specificity by EPEC," Hebrew University, Departments of Molecular Genetics and Biotechnology, Jerusalem, Conference on Epidemiology of VTEC, Malahide, Ireland, Feb. 8-10, 2001, website: www.research.teagasc.ie/vteceurope/PVpapers/rosenshinepv.html
4. Swerdlow, et al., "A waterborne outbreak in Missouri of Escherichia coli O157:H7 associated with bloody diarrhea and death," Annuals of Internal Medicine, 117:812-9, 1992.
About the author
Dr. Kelly A. Reynolds is a research scientist at the University of Arizona with a focus on development of rapid methods for detecting human the pathogenic viruses in drinking water. She holds a master of science degree in public health (MSPH) from University of South Florida and doctorate in microbiology from the University of Arizona. Reynolds also has been a member of the WC&P Technical Review Committee since 1997.