Induction of the Yersinia pestis PhoP-PhoQ Regulatory System in the Flea and Its Role in Producing a Transmissible Infection

Transmission of Yersinia pestis is greatly enhanced after it forms a bacterial biofilm in the foregut of the flea vector that inter-feres with normal blood feeding. Here we report that the ability to produce a normal foregut-blocking infection depends on in-duction of the Y. pestis PhoP-PhoQ two-component regulatory system in the flea. Y. pestis phoP-negative mutants achieved nor-mal infection rates and bacterial loads in the flea midgut but produced a less cohesive biofilm both in vitro and in the flea and had a greatly reduced ability to localize to and block the flea foregut. Thus, not only is the PhoP-PhoQ system induced in the flea gut environment, but also this induction is required to produce a normal transmissible infection. The altered biofilm phenotype in the flea was not due to lack of PhoPQ-dependent or PmrAB-dependent addition of aminoarabinose to the Y. pestis lipid A, because an aminoarabinose-deficient mutant that is highly sensitive to cationic antimicrobial peptides had a normal phenotype in the flea digestive tract. In addition to enhancing transmissibility, induction of the PhoP-PhoQ system in the arthropod vector prior to transmission may preadapt Y. pestis to resist the initial encounter with the mammalian innate immune response. Yersinia pestis, the causative agent of bubonic and pneumonicplague, is unique among the enteric group of Gram-negative bacteria in having adopted an arthropod-borne route of transmis-sion. During its life cycle, Y. pestis alternates between two eukary-otic hosts: a mammal (usually a rodent) and an insect (a flea). Y. pestis faces quite different physiological challenges in these dispa