LAUSR

Typhoid and paratyphoid fever are severe systemic infections caused by human-adapted typhoidal Salmonella serovars that are indistinguishable in their clinical presentation, but differ from human gastroenteritis caused by zoonotic non-typhoidal Salmonella serovars. Typhoidal Salmonella serovars evolved from ancestral gastrointestinal pathogens through genetic changes that supported a change in pathogen ecology. Typhoidal Salmonella serovars share virulence properties that were acquired through convergent evolution and therefore this group is not defined by the presence of shared virulence genes that are absent from non-typhoidal Salmonella serovars. One feature distinguishing typhoidal Salmonella serovars from gastrointestinal pathogens is their ability to avert the respiratory burst of neutrophils. Furthermore, typhoidal Salmonella serovars possess several mechanisms to moderate intestinal inflammation, which are absent from non-typhoidal Salmonella serovars. Collectively, these shared virulence mechanisms enable typhoidal Salmonella serovars to breach an intact mucosal barrier and reach the gall bladder, a new ecological niche that is important because chronic gall bladder carriage promotes disease transmission. Thus, the morbidity and mortality resulting from the severe systemic infection that enables typhoidal Salmonella serovars to reach the gall bladder is coupled to their capacity for infectious transmission, which is the principal driving force of natural selection directing the emergence of this pathovar.