Bacterial pathogen adaptation during human infections




Crofts, Alexander

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Like all organisms on earth, bacteria must adapt to changes in their environment to survive. Thus, discovering bacterial adaptations reveals the tools bacteria use to be successful. Identifying how pathogenic bacteria adapt during infections can consequently identify the tools bacteria use to cause disease, and therapy design can then consider inhibiting these tools to treat or prevent infections. Here, the ways in which two worldwide human intestinal pathogens, Campylobacter jejuni and Enterotoxigenic E. coli (ETEC), adapt to the human host during infections are explored. Bacteria were studied directly in infected samples from controlled human infection models. In C. jejuni, genetic adaptations that were selected for during acute and persistent human infections identified the role of a previously uncharacterized flagellar modification gene during persistence. In ETEC, the bacteria’s ability to sense oxygen was linked to global virulence gene expression in human infection samples as well as biofilm formation. As environmental ETEC biofilms are associated with seasonal ETEC epidemics, oxygen sensing likely contributes to human infection inside and outside of the host. Together, these data demonstrate the scope of pathogen adaptation during infections, identified new targetable virulence factors, and can thus aid the design of new therapies



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