Evolution of Salmonella within Hosts

Within-host evolution has resulted in thousands of variants of Salmonella that exhibit remarkable diversity in host range and disease outcome, from broad host range to exquisite host restriction, causing gastroenteritis to disseminated disease such as typhoid fever. Within-host evolution is a continuing process driven by genomic variation that occurs during each infection, potentiating adaptation to a new niche resulting from changes in animal husbandry, the use of antimicrobials, and emergence of immune compromised populations. We discuss key advances in our understanding of the evolution of Salmonella within the host, inferred from (i) the process of host adaptation of Salmonella pathovars in the past, and (ii) direct observation of the generation of variation and selection of beneficial traits during single infections. Highlights Salmonella is a bacterial pathogen with remarkable diversity in its host range and pathogenicity due to past within-host evolution in vertebrate species that modified ancestral mechanisms of pathogenesis. Variation arising during infection includes point mutations, new genes acquired through horizontal gene transfer (HGT), deletions, and genomic rearrangements. Beneficial mutations increase in frequency within the host and, if they retain the ability to be transmitted to subsequent hosts, may become fixed in the population. Whole-genome sequencing of sequential isolates from clinical infections reveals within-host HGT and point mutations that impact therapy and clinical management. HGT is the primary mechanism for evolution in prokaryotes and is synergised by complex networks of transfer involving the microbiome. Within-host evolution of Salmonella , resulting in new pathovars, can proceed in the absence of HGT.