Figure 7. The environment encountered by Y. pestis during its life cycle, and the response that produce an infection transmitted by the flea.

(A) Y. pestis experiences environment fluctuations in pH and osmolarity when it passes from the mammal’s blood into the arthropod vector and vice versa, and (according to our present data) also while it colonizes the flea gut. (B) In response to nutrient depletion and (perhaps) acidic pH, the EnvZ and PhoQ sensors self-phosphorylate and then transfer the phosphate to their cognate regulators OmpR and PhoQ, which sets in motion a molecular program needed to block the flea (e.g. ompF, and a gene X that has yet to be identified) (this study, and Rebeil et al., 2013 Vadyvaloo et al., 2015). The molecular program (unknown gene Y) activated by PhoQ to block fleas is unknown, while OmpR’s molecular program includes ompF and other loci (perhaps including phoPQ; this study and Gao et al., 2011b). The photo on the left represents a blocked flea, which is characterized by the presence of fresh red blood in the foregut (at the right of the circle) but not in the midgut (at the left of the cycle). The photo on the right shows the infected flea gut, which is blocked by a mass containing a myriad of Y. pestis (green). The mass extends from the esophagus (E) to the proventriculus (PV) and the midgut (MG). Genes X and Y have yet to be identified.