A critical role for staphylococcal nitric oxide synthase in controlling flavohemoglobin toxicity.

Autor: Singh RM; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Chaudhari SS; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Panda S; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Hutfless EH; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Heim CE; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Shinde D; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Alqarzaee AA; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Sladek M; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Kumar V; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Zimmerman MC; Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Fey PD; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Kielian T; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA., Thomas VC; Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA. Electronic address: vinai.thomas@unmc.edu.
Jazyk: angličtina
Zdroj: Redox biology [Redox Biol] 2023 Nov; Vol. 67, pp. 102935. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1016/j.redox.2023.102935
Abstrakt: Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. However, in the absence of nitrosative stress, Hmp generates significant amounts of the harmful superoxide radical (O 2 •- ) from its heme prosthetic group which impedes growth. To limit Hmp toxicity, nitrite (NO 2 - ) derived from seNOS promotes CymR-CysK regulatory complex activity, which typically regulates cysteine metabolism, but we now demonstrate to also repress hmp transcription. These findings reveal a critical mechanism through which the bacterial NOS-Hmp axis drives staphylococcal fitness.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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