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Previous work concluded that the stringent response and the sigma factor RpoS are essential for the survival of <jats:italic>Lp<\/jats:italic> in water. In the present study, we investigated the role of the LetA\/S two-component signal transduction system in the successful survival of <jats:italic>Lp<\/jats:italic> in water. In addition to cell size reduction in the post-exponential phase, LetS also contributes to cell size reduction when <jats:italic>Lp<\/jats:italic> is exposed to water. Importantly, absence of the sensor kinase results in a significantly lower survival as measured by CFUs in water at various temperatures and an increased sensitivity to heat shock. According to the transcriptomic analysis, LetA\/S orchestrates a general transcriptomic downshift of major metabolic pathways upon exposure to water leading to better culturability, and likely survival, suggesting a potential link with the stringent response. However, the expression of the LetA\/S regulated small regulatory RNAs, RsmY and RsmZ, is not changed in a <jats:italic>relAspoT<\/jats:italic> mutant, which indicates that the stringent response and the LetA\/S response are two distinct regulatory systems contributing to the survival of <jats:italic>Lp<\/jats:italic> in water.<\/jats:p>","DOI":"10.1038\/s41598-018-24263-9","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T15:05:49Z","timestamp":1524582349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The LetA\/S two-component system regulates transcriptomic changes that are essential for the culturability of Legionella pneumophila in water"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1699-9536","authenticated-orcid":false,"given":"Nilmini","family":"Mendis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"McBride","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Saoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thangadurai","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien P.","family":"Faucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"24263_CR1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1128\/aem.41.1.9-16.1981","volume":"41","author":"CB Fliermans","year":"1981","unstructured":"Fliermans, C. 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