Dataset Information

The NagY regulator: A member of the BglG/SacY antiterminator family conserved in Enterococcus faecalis and involved in virulence.

ABSTRACT: Enterococcus faecalis is a commensal bacterium of the gastrointestinal tract but also a major nosocomial pathogen. This bacterium uses regulators like BglG/SacY family of transcriptional antiterminators to adapt its metabolism during host colonization. In this report, we investigated the role of the BglG/SacY family antiterminator NagY in the regulation of the nagY-nagE operon in presence of N-acetylglucosamine, with nagE encoding a transporter of this carbohydrate, as well as the expression of the virulence factor HylA. We showed that this last protein is involved in biofilm formation and glycosaminoglycans degradation that are important features in bacterial infection, confirmed in the Galleria mellonella model. In order to elucidate the evolution of these actors, we performed phylogenomic analyses on E. faecalis and Enterococcaceae genomes, identified orthologous sequences of NagY, NagE, and HylA, and we report their taxonomic distribution. The study of the conservation of the upstream region of nagY and hylA genes showed that the molecular mechanism of NagY regulation involves ribonucleic antiterminator sequence overlapping a rho-independent terminator, suggesting a regulation conforming to the canonical model of BglG/SacY family antiterminators. In the perspective of opportunism understanding, we offer new insights into the mechanism of host sensing thanks to the NagY antiterminator and its targets expression.

SUBMITTER: Soussan D

PROVIDER: S-EPMC9981650 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The NagY regulator: A member of the BglG/SacY antiterminator family conserved in Enterococcus faecalis and involved in virulence.

Soussan Diane D Salze Marine M Ledormand Pierre P Sauvageot Nicolas N Boukerb Amine A Lesouhaitier Olivier O Fichant Gwennaele G Rincé Alain A Quentin Yves Y Muller Cécile C

Frontiers in microbiology 20230217

Enterococcus faecalis is a commensal bacterium of the gastrointestinal tract but also a major nosocomial pathogen. This bacterium uses regulators like BglG/SacY family of transcriptional antiterminators to adapt its metabolism during host colonization. In this report, we investigated the role of the BglG/SacY family antiterminator NagY in the regulation of the nagY-nagE operon in presence of N-acetylglucosamine, with nagE encoding a transporter of this carbohydrate, as well ...[more]

PMID: 36875533

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Project description:Manganese (Mn) is an essential micronutrient that is not readily available to pathogens during infection due to an active host defense mechanism known as nutritional immunity. To overcome this nutrient restriction, bacteria utilize high-affinity transporters that allow them to compete with host metal-binding proteins. Despite the established role of Mn in bacterial pathogenesis, little is known about the relevance of Mn in the pathophysiology of E. faecalis. Here, we identified and characterized the major Mn acquisition systems of E. faecalis. We discovered that the ABC-type permease EfaCBA and two Nramp-type transporters, named MntH1 and MntH2, work collectively to promote cell growth under Mn-restricted conditions. The simultaneous inactivation of EfaCBA, MntH1 and MntH2 (ΔefaΔmntH1ΔmntH2 strain) led to drastic reductions (>95%) in cellular Mn content, severe growth defects in body fluids (serum and urine) ex vivo, significant loss of virulence in Galleria mellonella, and virtually complete loss of virulence in rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI) models. Despite the functional redundancy of EfaCBA, MntH1 and MntH2 under in vitro or ex vivo conditions and in the invertebrate model, dual inactivation of efaCBA and mntH2 (ΔefaΔmntH2 strain) was sufficient to prompt maximal sensitivity to calprotectin, a Mn- and Zn-chelating host antimicrobial protein, and for the loss of virulence in mammalian models. Interestingly, EfaCBA appears to play a prominent role during systemic infection, whereas MntH2 was more important during CAUTI. The different roles of EfaCBA and MntH2 in these sites could be attributed, at least in part, to the differential expression of efaA and mntH2 in cells isolated from hearts or from bladders. Collectively, this study demonstrates that Mn acquisition is essential for the pathogenesis of E. faecalis and validates Mn uptake systems as promising targets for the development of new antimicrobials.

Dataset Information

The NagY regulator: A member of the BglG/SacY antiterminator family conserved in Enterococcus faecalis and involved in virulence.

Publications

The NagY regulator: A member of the BglG/SacY antiterminator family conserved in <i>Enterococcus faecalis</i> and involved in virulence.

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