BOX WO-2Host-Restriction Versus Virulence in Bordetella spp.

Genomic comparisons of three Bordetella species by workshop presenter Julian Parkhill and colleagues provide clues to the evolution of virulence in bacterial pathogens (Parkhill et al., 2003). B. pertussis, the primary causative agent of whooping cough in humans, can survive only within its single host species. B. parapertussis also causes whooping cough; some strains are restricted to humans, others to sheep. Both of these species have apparently evolved from the less virulent B. bronchiseptica, which causes chronic and often asymptomatic disease in a wide range of animals. These three species are genetically identical at the 16S RNA level. By most measures (except phenotype), they constitute a single species.

There is little sequence variation among strains of either B. pertussis or B. parapertussis worldwide, indicating that these species are very recently evolved; by contrast, B. bronchiseptica strains vary considerably. Their genome structures also differ significantly: compared with B. bronchiseptica, the B. pertussis genome is approximately 25 percent smaller and contains a large number of genes inactivated by mutation (pseudogenes). A large majority of these pseudogenes resulted from single mutations, indicating that they were recently inactivated (since further mutations have not accumulated in the inactive gene). Approximately one-third of the pseudogenes in B. pertussis were inactivated by an insertion sequence (IS) element, a mobile genetic sequence that, once introduced into a bacterial ge-nome, can reproduce and reinsert in multiple locations. The B. pertussis genome contains 240 copies of a single IS element, which have undoubtedly produced high levels of recombination and deletion. B. parapertussis contains different IS elements that have also proliferated in its genome.

In evolving from B. bronchisepticatoward host restriction and greater virulence, B. pertussis and B. parapertussis did not acquire novel virulence factors, but instead lost function in genes associated with host interaction (thereby narrowing their host ranges) and in regulation of the expression of virulence factors, such as the pertussis toxin. Parkhill and coworkers hypothesize that these changes occurred when humans began living in close proximity to each other, increasing opportunities for pathogen transmission, and easing selection against virulence (which formerly might have killed a host before it could transmit the pathogen). These circumstances could have created an evolutionary bottleneck, causing the increased fixation of advantageous (and potentially disadvantageous) point mutations and IS element insertions in the population, giving rise to the new, more virulent, and host-restricted species.

Similar events appear to have influenced the evolution of a variety of human pathogens, including S. typhi and S. paratyphi, independent derivatives of the ancestral S. enterica, and Yersinia pestis, the causative agent of plague, from its ancestor Y. pseudotuberculosis. An evolutionary bottleneck—perhaps the result of domestication—may also have enabled the descent of Burkholderia mallei, a pathogen restricted to horses, which causes glanders, from B. pseudomallei, a broad host-range pathogen. Likewise, the planting of crops as monocultures may have separated Clavibacter michiganensis subspecies sepedonicus, an endophytic pathogen of potato with a narrow host range, from C. michiganensis subspecies michiganensis, an epiphytic pathogen with a broad host range.

From: Workshop Overview

Cover of Microbial Evolution and Co-Adaptation
Microbial Evolution and Co-Adaptation: A Tribute to the Life and Scientific Legacies of Joshua Lederberg: Workshop Summary.
Institute of Medicine (US) Forum on Microbial Threats.
Washington (DC): National Academies Press (US); 2009.
Copyright © 2009, National Academy of Sciences.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.