FEATURE ARTICLE
The Evolutionary Ecology of Escherichia coli
Abundantly studied and much feared, E. coli has more genomic plasticity than once believed and may have followed various routes to become a pathogen
Valeria Souza, Amanda Castillo, Luis Eguiarte
Mutation and Pathogenesis
Recently, the study of mutation in microorganisms has taken on an interesting character. First there was the controversy over "directed mutation." Patterns of mutation were seen in bacteria that seemed less than random; were certain types of mutations favored over others? This debate, which began in 1989, was put to rest by studies whose results strongly contradicted this notion. But in 1996, a different question of mutation pattern surfaced when J. Eugene Leclerc and his colleagues at the U.S. Food and Drug Administration found that pathogenic bacteria such as O157:H7 are "hypermutable": They exhibit a much higher mutation rate than nonpathogens. According to Leclerc's proposition, errors in the DNA repair system may constitute a lifestyle adaptation that helps the bacteria escape the immune system of their hosts. The challenges of life as a pathogen may select for "mutators," variants that possess the ability to mutate rapidly during invasion, colonization and immune warfare. A year later, however, another study found the frequency of mutator strains to be similar between commensal and pathogenic E. coli in human beings.
The findings came in the midst of intense interest in the rise of antibiotic resistance. Resistance to antibiotic drugs appears to arise mainly through the sharing of resistance plasmids via conjugation. But high mutation rates might also play a role, and the idea continues to be hotly debated. Some studies of experimental evolution indicate that only under certain conditions can bacteria reach anomalously high mutation rates, especially in changing environments and small populations. Travis Kibota of Clark College and Michael Lynch of the University of Oregon presented in 1996 a model where hypermutability itself is always unstable, since there are more deleterious mutations than there are those that either carry pathogenicity, or are adaptive and provide escape from the host's attack.
Recently Antonio Oliver and his colleagues at INSALUD, Spain's National Institute of Health, studied patients with cystic fibrosis who were subjected at various ages to high doses of antibiotics to combat the bacterium Pseudomonas aeruginosa. The P. aeruginosa of these patients displayed a significant number of hypermutations associated with gravely ill patients with other diseases. From this they proposed in 2000 that hypermutation is an adaptation that permits sufficient resistance to antibiotics for survival in the altered lung mucosa of a patient with this disease.
In E. coli we can compare evolutionary patterns between pathogenic and nonpathogenic strains by looking at pathogenic islands in the genome. Much work is being done to understand the evolution of a pathogenic island called the locus of enterocyte effacement, or LEE, which contains a group of genes that enable the bacterium to create lesions in the intestinal lining. We are currently conducting such comparisons by studying a part of the IECOL collection. There seems not to be any correlation between mutation rate and presence of the LEE or elements of this island, but we have begun to learn about other aspects of how bacteria acquire pathogenic abilities.
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