<i>Yersinia pestis</i> BipA is a novel regulator of pesticin and a type 6 secretion system

<i>Yersinia pestis</i> is a gram-negative bacterium and the causative agent of bubonic, septicemic, and pneumonic plague. <i>Y. pestis</i> is most commonly transmitted to humans by infected fleas that deposit the bacteria into the dermis at the bite site, leading to bubonic plague. The bacteria ultimately access the bloodstream, and after deposition in the lung, can be transmitted person-to-person through infectious respiratory droplets, resulting in primary pneumonic plague, a highly lethal and rapidly progressing pneumonia. Pathogenesis is mediated by a suite of chromosomally encoded and plasmid-borne virulence factors, and infection is maintained by temperature-dependent coordinated modifications in gene expression that facilitate bacterial survival in both the flea and mammalian hosts. BipA (BPI-inducible protein A) is a highly conserved translational GTPase that is a <i>Y. pestis</i> virulence factor. BipA modulates protein expression under stress conditions, and its deletion renders <i>Y. pestis</i> more sensitive to killing by neutrophils and attenuates bacterial growth in a murine infection model of pneumonic plague. In the work described here, we show that BipA also regulates specific <i>Y. pestis</i> proteins at flea/environmental temperatures. We show that BipA is responsible for the induction of a recently described type 6 secretion system (T6SS), as well as the transcriptional regulator RovC. We also show that BipA regulates the production of the known <i>Y. pestis</i> bacteriocin pesticin, and that bacteria lacking BipA have a defect in competition not solely attributable to the T6SS or pesticin. Our results show that in addition to its role in the mammalian host, regulation of specific proteins by BipA also likely contributes to bacterial survival during the flea/environmental phase, where <i>Y. pestis</i> must compete with other species of bacteria within a particular niche.