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Here, we report that both the acidic pH and osmolarity of the lumen\u2019s contents display simple harmonic oscillations with different periods. Since an acidic pH and osmolarity are two of three known stimuli of the OmpR\u2010EnvZ two\u2010component system in bacteria, we investigated the role and function of this <jats:italic>Y. pestis<\/jats:italic> system in fleas. By monitoring the <jats:italic>in vivo<\/jats:italic> expression pattern of three OmpR\u2010EnvZ\u2010regulated genes, we concluded that the flea gut environment triggers OmpR\u2010EnvZ. 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\u2010EnvZ). Lastly, we found that the OmpR\u2010EnvZ and the OmpF porin are needed to produce the biofilm that ultimately obstructs the flea\u2019s gut and thus hastens the flea\u2010borne transmission of plague. Taken as a whole, our data suggest that the flea gut is a complex, fluctuating environment in which <jats:italic>Y. pestis<\/jats:italic> senses nutrient depletion via OmpR\u2010EnvZ. Once activated, the latter triggers a molecular program (including at least OmpF) that produces the biofilm required for efficient plague transmission.<\/jats:p>","DOI":"10.1111\/mmi.14372","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T13:19:13Z","timestamp":1566220753000},"page":"1471-1482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Nutrient depletion may trigger the <i>Yersinia pestis<\/i> OmpR\u2010EnvZ regulatory system to promote flea\u2010borne plague transmission"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1834-5416","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Bontemps\u2010Gallo","sequence":"first","affiliation":[{"name":"University of Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille U1019\u2010UMR8204, CIIL\u2010Center for Infection and Immunity of Lille F\u201059000 Lille 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