A TetR-like transcriptional regulator in Stenotrophomonas maltophilia involved in fatty acid metabolism is controlled by quorum sensing signals

Coves, X.; Huedo, P.; Bravo, M.; Conchillo-Sole, O.; Gomez, A.-C.; Esteve-Codina, A.; Dabad, M.; Gut, M.; Daura, X.; Yero, D.; Gibert, I.

doi:10.1101/2022.08.31.506136

bioRxiv · 10.1101/2022.08.31.506136

A TetR-like transcriptional regulator in Stenotrophomonas maltophilia involved in fatty acid metabolism is controlled by quorum sensing signals

Coves, X.·Huedo, P.·Bravo, M.·Conchillo-Sole, O.·Gomez, A.-C.·Esteve-Codina, A.·Dabad, M.·Gut, M.·Daura, X.·Yero, D.·Gibert, I.

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Abstract

Stenotrophomonas maltophilia is an environmental bacterium and it is also an emerging opportunistic multidrug-resistant pathogen. It uses the endogenous DSF quorum sensing (QS) system to coordinate population behaviors and to regulate virulence processes but can also respond to exogenous AHL signals produced by neighboring bacteria. Whole-transcriptome sequencing analyses were performed for S. maltophilia K279a in the exponential and stationary phases as well as in exponential cultures after treatment with exogenous DSF or AHLs. The results revealed that at the beginning of the stationary phase 1673 genes are differentially expressed. COG analysis showed that most of these genes were enriched for energetic metabolism processes and regulation of gene expression. After adding DSF or AHLs, 28 or 82 genes were found deregulated, respectively, 22 of which upregulated by both autoinducers. Interestingly, among these later genes, 14 were also upregulated in the stationary phase. Gene functions regulated by all conditions include lipid and amino acid metabolism, stress response and signal transduction, nitrogen and iron metabolism, and adaptation to microoxic conditions. Among the common top upregulated QS core genes, a putative TetR-like regulator (Smlt2053) was selected for functional characterization. This regulator has been shown to control a narrow regulon, including its own operon. It was found to sense long-chain fatty acids, including the QS signal DSF, and regulate a {beta}-oxidation catabolic pathway. Overall, our findings provide clues on the role that the QS could have in S. maltophilia in the transition from the exponential to the stationary phase and bacterial fitness under high-density growth. IMPORTANCEThe quorum sensing system in Stenotrophomonas maltophilia, in addition to coordinating the bacterial population, controls virulence-associated phenotypes, such as biofilm formation, motility, protease production, and antibiotic resistance mechanisms. Biofilm formation is frequently associated with the persistence and chronic nature of nosocomial infections. In addition, biofilms exhibit high resistance to antibiotics, making treatment of these infections extremely difficult. The importance of studying the metabolic and regulatory systems controlled by quorum sensing autoinducers will make it possible to discover new targets to control pathogenicity mechanisms in S. maltophilia.

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Coves, X., Huedo, P., Bravo, M., Conchillo-Sole, O., Gomez, A.-C., Esteve-Codina, A., Dabad, M., Gut, M., Daura, X., Yero, D., Gibert, I.. 2022-09-03. A TetR-like transcriptional regulator in Stenotrophomonas maltophilia involved in fatty acid metabolism is controlled by quorum sensing signals. https://doi.org/10.1101/2022.08.31.506136

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