A plasmid locus associated withKlebsiellaclinical infections encodes a microbiome-dependent gut fitness factor

Introductory paragraph Gut colonization by the pathogen Klebsiella pneumoniae (Kp) is consistently associated with subsequent Kp disease 1-5 , and patients are predominantly infected with their colonizing strain 1,2 . However, colonizing strains likely vary in their potential to cause infection. We previously identified the plasmid-encoded tellurium resistance ( ter ) operon as highly associated with infection when compared to asymptomatic colonization in hospitalized patients 1 . The ter operon bestows resistance to the toxic compound tellurite oxide (TeO 3 −2 ), but this is unlikely to be its physiological function, as tellurium and TeO 3 −2 are exceedingly rare. Here we show that terC is necessary and terZABCDEF is sufficient for phenotypic TeO 3 −2 resistance. Next, we demonstrate that ter is encoded on a diverse group of plasmids without known plasmid-encoded virulence genes, suggesting an independent role in infection. Finally, our studies indicate that ter is a gut fitness factor, and its fitness advantage is conferred only when specific gut microbiota constituents are present. Collectively, these data reveal the Kp ter operon that is highly associated with human infection likely acts early in pathogenesis as a horizontally-transferrable fitness factor promoting robust gut colonization in the presence of the indigenous microbiota.