Nutrient depletion may trigger the Yersinia pestis OmpR‐EnvZ regulatory system to promote flea‐borne plague transmission

Abstract

The flea's lumen gut is a poorly documented environment where the agent of flea-borne plague, Yersinia pestis, must replicate to produce a transmissible infection. Here, we report that both the acidic pH and osmolarity of the lumen's contents display simple harmonic oscillations with different periods. Since an acidic pH and osmolarity are two of three known stimuli of the OmpR-EnvZ two-component system in bacteria, we investigated the role and function of this Y. pestis system in fleas. By monitoring the in vivo expression pattern of three OmpR-EnvZregulated genes, we concluded that the flea gut environment triggers OmpR-EnvZ. This activation was not, however, correlated with changes in pH and osmolarity but matched the pattern of nutrient depletion (the third known stimulus for OmpR-EnvZ). Lastly, we found that the OmpR-EnvZ and the OmpF porin are needed to produce the biofilm that ultimately obstructs the flea's gut and thus hastens the flea-borne transmission of plague. Taken as a whole, our data suggest that the flea gut is a complex, fluctuating environment in which Y. pestis senses nutrient depletion via OmpR-EnvZ. Once activated, the latter triggers a molecular program (including at least OmpF) that produces the biofilm required for efficient plague transmission. ; Tel 33 320 871 193; Fax 33 320 871 178. § Bontemps-Gallo and Fernandez contributed equally to this work.

The Regulator OmpR in Yersinia enterocolitica Participates in Iron Homeostasis by Modulating Fur Level and Affecting the Expression of Genes Involved in Iron Uptake

“…It can regulate transcription in a positive or negative way by binding to consensus sequence elements that occur at different locations in promoter regions [ 54 , 55 , 56 ]. It has been shown that the EnvZ/OmpR system modulates the expression of numerous genes in response to environmental changes such as altered osmolarity, pH and nutrient content [ 57 , 58 , 59 , 60 , 61 , 62 ]. The transcriptional regulator OmpR has been best studied for its role in the inverse osmoregulation of the outer membrane porins OmpC and OmpF in E. coli .…”

Molecular and Genetic Mechanisms That Mediate Transmission of Yersinia pestis by Fleas

“…Some fleas, particularly those that feed frequently, such as the cat flea Ctenocephalides felis , excrete undigested and partially digested portions of their blood meal during or soon after feeding [ 7 ]. The midgut pH fluctuates between about 6.5 and 7 at different times after a blood meal, and osmolarity drops from around 500 to 300 mOsm, gradually increasing over the next 24 h to the original value as digestion proceeds [ 8 ]. The flea gut is aerobic, oxygenated by an extensive abdominal trachea system that is maximally active during blood digestion [ 9 ].…”

“…If the PhoPQ system is nonfunctional, several other general and acid stress response genes are upregulated in the flea [ 28 ]. As the flea digests and absorbs blood meal elements, the osmolarity of the midgut contents increases [ 8 ], and several Y. pestis genes with osmoadaptive and osmoprotective functions are upregulated [ 25 , 27 , 29 , 74 ]. The stress-sensing alternative sigma factor, RpoE, is also upregulated in the flea [ 25 ].…”

The Diverse Roles of the Global Transcriptional Regulator PhoP in the Lifecycle of Yersinia pestis

“…Mildly acidic pH (~6.6) and hyperosmolarity (~500 mOsm) of the flea gut milieu are considered to be the stress signals encountered by Y. pestis during insect infection [ 66 , 67 ]. PhoP expression is closely linked to management of these stresses in the flea gut, as demonstrated in comparative transcriptomic studies between a phoP mutant and wild-type strain during flea infection [ 64 ].…”