Acquisition of genes and gene clusters can drive the rapid evolution of pathogens and turn nonpathogens into pathogens. Consider, for example, Vibrio cholerae—the Gram-negative bacterium that causes the epidemic diarrheal disease cholera. Of the hundreds of strains of Vibrio cholerae, the only ones that cause pandemic human disease are those infected with a mobile bacteriophage (CTXϕ) containing genes encoding the two subunits of the toxin that causes the diarrhea. As summarized in Figure 23–5, seven pandemics of V. cholerae have arisen since 1817. The first six were caused by the periodic reemergence of so-called Classical strains. In addition to the toxin-encoding bacteriophage, these Classical strains shared a similar O1 surface antigen, part of the LPS in the outer membrane (see Figure 23–3C). In 1961, the seventh pandemic began, caused by a new strain named “El Tor,” which arose when an O1-expressing strain acquired two bacteriophages and at least two new pathogenicity islands. El Tor eventually displaced the Classical strains. In 1992, a new strain emerged in which O1 was replaced with another O-antigen variant called O139, which was not recognized by antibodies present in the blood of survivors of previous cholera epidemics. The O139 strain also contains a transposon-like element that encodes antibiotic resistance. As this example makes clear, the rapid evolution of bacterial pathogens can be likened to an arms race which pits the survival of a bacterium against our immune systems and the tools of modern medicine. Similar struggles for survival take place between all pathogens and humans, and understanding these conflicts provides key insights into the evolution of pathogens and greatly informs us how we treat new outbreaks of infectious diseases.
Bacterial Virulence Genes Encode Effector Proteins and Secretion Systems to Deliver Effector Proteins to Host Cells
What are the gene products that enable a bacterium to cause disease in a healthy host? For pathogenic bacteria that live outside of host cells, called extracellular
Figure 23–5 Comparative-genomicsbased model for the evolution of pathogenic Vibrio cholerae strains.
Progenitor strains in the wild first acquired the biosynthetic pathway necessary to make the O1 antigen type of carbohydrate chain on the outer-membrane lipopolysaccharide (see Figure 23–3C). Incorporation of the CTXϕ bacteriophage created the Classical pathogenic strains responsible for the first six worldwide epidemics of cholera between 1817 and 1923. Sometime in the twentieth century, an O1 strain in the environment picked up the CTXϕ bacteriophage again, along with an associated bacteriophage RS1ϕ and two pathogenicity islands (VSP1 and VSP2), creating the El Tor strain that emerged as the seventh worldwide pandemic in 1961. In 1992, an El Tor strain was isolated that had picked up a new DNA cassette, enabling it to produce the O139 antigen type of carbohydrate chain rather than the O1 type. This altered the bacterium’s interaction with the human immune system, without diminishing its virulence; this bacterium also picked up a new pathogenicity island (SXT). An electron micrograph of Vibrio cholerae (V. cholerae) is shown in Figure 23–2B.