Role of the PhoP-PhoQ Gene Regulatory System in Adaptation of Yersinia pestis to Environmental Stress in the Flea Digestive Tract

The Yersinia pestis PhoPQ gene regulatory system is induced during infection of the flea digestive tract and is required to produce adherent biofilm in the foregut, which greatly enhances bacterial transmission during a flea bite. To understand the in vivo context of PhoPQ induction and to determine PhoP-regulated targets in the flea, we undertook whole genome comparative transcriptional profiling of Y. pestis wild-type and ΔphoP strains isolated from infected fleas and from temperature-matched in vitro planktonic and flowcell biofilm cultures. In the absence of PhoP regulation, the gene expression program indicated that the bacteria experience diverse physiological stresses and are in a metabolically less active state. Multiple stress response genes, including several toxin-antitoxin loci and YhcN family genes responsible for increased acid tolerance, were upregulated in the phoP mutant during flea infection. The data imply that PhoPQ is induced by low pH in the flea gut, and that PhoP modulates physiologic adaptation to acid and other stresses encountered during infection of the flea. This adaptive response, together with PhoP-dependent modification of the bacterial outer surface that includes repression of pH 6 antigen fimbriae, supports stable biofilm development in the flea foregut. Yersinia pestis wild type vs. phoP mutant at various growth conditions