Dual quorum-sensing control of purine biosynthesis drives pathogenic fitness of Enterococcus faecalis .

Autor:	Zlitni S; Department of Genetics, Stanford University, Stanford, CA, USA.; Department of Medicine (Hematology, Blood and Marrow Transplantation), Stanford University, Stanford, CA, USA., Bowden S; Department of Genetics, Stanford University, Stanford, CA, USA., Sberro H; Department of Genetics, Stanford University, Stanford, CA, USA.; Department of Medicine (Hematology, Blood and Marrow Transplantation), Stanford University, Stanford, CA, USA., Torres MDT; Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA.; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA.; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.; Penn Institute for Computational Science, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA., Vaughan JM; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, San Diego, CA, USA., Pinto AFM; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, San Diego, CA, USA., Pinto Y; Department of Genetics, Stanford University, Stanford, CA, USA.; Department of Medicine (Hematology, Blood and Marrow Transplantation), Stanford University, Stanford, CA, USA., Fernandez D; Program in Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.; Sarafan ChEM-H Macromolecular Structure Knowledge Center, Stanford University, Stanford, CA 94305, USA., Röst H; Department of Molecular Genetics, Donnelly Centre for Cellular and Biomolecular Research, The University of Toronto, Toronto, ON, Canada., Saghatelian A; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, San Diego, CA, USA., de la Fuente-Nunez C; Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA.; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA.; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.; Penn Institute for Computational Science, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA., Bhatt AS; Department of Genetics, Stanford University, Stanford, CA, USA.; Department of Medicine (Hematology, Blood and Marrow Transplantation), Stanford University, Stanford, CA, USA.; Lead contact.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 13. Date of Electronic Publication: 2024 Aug 13.
DOI:	10.1101/2024.08.13.607696
Abstrakt:	Enterococcus faecalis is a resident of the human gut, though upon translocation to the blood or body tissues, it can be pathogenic. Here we discover and characterize two peptide-based quorum-sensing systems that transcriptionally modulate de novo purine biosynthesis in E. faecalis . Using a comparative genomic analysis, we find that most enterococcal species do not encode this system; E. moraviensis , E. haemoperoxidus and E. caccae , three species that are closely related to E. faecalis , encode one of the two systems, and only E. faecalis encodes both systems. We show that these systems are important for the intracellular survival of E. faecalis within macrophages and for the fitness of E. faecalis in a murine wound infection model. Taken together, we combine comparative genomics, microbiological, bacterial genetics, transcriptomics, targeted proteomics and animal model experiments to describe a paired quorum sensing mechanism that directly influences central metabolism and impacts the pathogenicity of E. faecalis . Competing Interests: Declaration of Interests Cesar de la Fuente-Nunez provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L., Peptidus, and Phare Bio. De la Fuente is also on the Advisory Board of the Peptide Drug Hunting Consortium (PDHC). The de la Fuente Lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work.
Databáze:	MEDLINE
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