Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

Autor:	Podkowik M; Department of Medicine, Division of Infectious Diseases, NYU Grossman School of Medicine, New York, United States.; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States., Perault AI; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Department of Microbiology, NYU Grossman School of Medicine, New York, United States., Putzel G; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Department of Microbiology, NYU Grossman School of Medicine, New York, United States.; Microbial Computational Genomic Core Lab, NYU Grossman School of Medicine, New York, United States., Pountain A; Institute for Systems Genetics; NYU Grossman School of Medicine, New York, United States., Kim J; Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, United States., DuMont AL; Department of Medicine, Division of Infectious Diseases, NYU Grossman School of Medicine, New York, United States., Zwack EE; Department of Microbiology, NYU Grossman School of Medicine, New York, United States., Ulrich RJ; Department of Medicine, Division of Infectious Diseases, NYU Grossman School of Medicine, New York, United States., Karagounis TK; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Ronald O. Perelman Department of Dermatology; NYU Grossman School of Medicine, New York, United States., Zhou C; Department of Medicine, Division of Infectious Diseases, NYU Grossman School of Medicine, New York, United States.; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States., Haag AF; School of Medicine, University of St Andrews, St Andrews, United Kingdom., Shenderovich J; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Department of Microbiology, NYU Grossman School of Medicine, New York, United States., Wasserman GA; Department of Surgery, Northwell Health Lenox Hill Hospital, New York, United States., Kwon J; Department of Medicine, Division of Infectious Diseases, NYU Grossman School of Medicine, New York, United States., Chen J; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Richardson AR; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States., Weiser JN; Department of Microbiology, NYU Grossman School of Medicine, New York, United States., Nowosad CR; Department of Pathology, NYU Grossman School of Medicine, New York, United States., Lun DS; Center for Computational and Integrative Biology and Department of Computer Science, Rutgers University, Camden, United States., Parker D; Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, United States., Pironti A; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Department of Microbiology, NYU Grossman School of Medicine, New York, United States.; Microbial Computational Genomic Core Lab, NYU Grossman School of Medicine, New York, United States., Zhao X; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China., Drlica K; Public Health Research Institute, New Jersey Medical School, Rutgers University, New Yprk, United States.; Department of Microbiology, Biochemistry & Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, United States., Yanai I; Institute for Systems Genetics; NYU Grossman School of Medicine, New York, United States.; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, United States., Torres VJ; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Department of Microbiology, NYU Grossman School of Medicine, New York, United States., Shopsin B; Department of Medicine, Division of Infectious Diseases, NYU Grossman School of Medicine, New York, United States.; Antimicrobial-Resistant Pathogens Program, New York University School of Medicine, New York, United States.; Department of Microbiology, NYU Grossman School of Medicine, New York, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Apr 30; Vol. 12. Date of Electronic Publication: 2024 Apr 30.
DOI:	10.7554/eLife.89098
Abstrakt:	The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H 2 O 2 , a crucial host defense against S. aureus . We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δ agr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δ agr strains to lethal H 2 O 2 doses. Increased survival of wild-type agr cells during H 2 O 2 exposure required sodA , which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δ agr cells from killing by H 2 O 2 . Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr -mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient ( Cybb -/- ) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage. Competing Interests: MP, AP, GP, AP, JK, EZ, RU, TK, CZ, AH, JS, GW, JK, JC, AR, JW, CN, DL, DP, AP, XZ, KD, IY No competing interests declared, AD Inventor on patents and patent applications (US8431, 687B2; US2019135900 A1; EP4313303A1) filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc provides research funding and other payments associated with a licensing agreement. These patents pertain solely to the development of vaccines and therapeutics targeting S. aureus toxins and are unrelated to the content presented in this work, VT Has received honoraria from Pfizer and MedImmune, and is an inventor on patents and patent applications filed by New York University,(US8431, 687B2; US2019135900 A1; EP4313303A1) which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc provides research funding and other payments associated with a licensing agreement, BS Has consulted for Basilea Pharmaceutica (© 2023, Podkowik et al.)
Databáze:	MEDLINE
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