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Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute


Listeria monocytogenes is ubiquitously present in the environment, highly adaptable and tolerant to various stresses. L. monocytogenes is also a foodborne pathogen associated with the largest foodborne outbreaks in recent US history. Signaling pathways involving the second messenger c-di-GMP play important roles in increased stress survival of proteobacteria and mycobacteria, yet roles of c-di-GMP signaling pathways in L. monocytogenes have remained unexplored. Here, we identified and systematically characterized functions of the proteins involved in c-di-GMP synthesis, degradation and sensing. We show that elevated c-di-GMP levels in L. monocytogenes result in synthesis of a previously unknown exopolysaccharide that promotes cell aggregation, inhibits motility in semi-solid media, and importantly, enhances bacterial tolerance to commonly used disinfectants as well as desiccation. These properties of the exopolysaccharide may increase listerial survival in food processing plants as well as on produce during transportation and storage. Elevated c-di-GMP levels also grossly diminish listerial invasiveness in enterocytes in vitro, and impair bacterial accumulation in selected mouse organs during oral infection.


Vyšlo v časopise: Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004301
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004301

Souhrn

Listeria monocytogenes is ubiquitously present in the environment, highly adaptable and tolerant to various stresses. L. monocytogenes is also a foodborne pathogen associated with the largest foodborne outbreaks in recent US history. Signaling pathways involving the second messenger c-di-GMP play important roles in increased stress survival of proteobacteria and mycobacteria, yet roles of c-di-GMP signaling pathways in L. monocytogenes have remained unexplored. Here, we identified and systematically characterized functions of the proteins involved in c-di-GMP synthesis, degradation and sensing. We show that elevated c-di-GMP levels in L. monocytogenes result in synthesis of a previously unknown exopolysaccharide that promotes cell aggregation, inhibits motility in semi-solid media, and importantly, enhances bacterial tolerance to commonly used disinfectants as well as desiccation. These properties of the exopolysaccharide may increase listerial survival in food processing plants as well as on produce during transportation and storage. Elevated c-di-GMP levels also grossly diminish listerial invasiveness in enterocytes in vitro, and impair bacterial accumulation in selected mouse organs during oral infection.


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