A Critical Role for Staphylococcal Nitric Oxide Synthase in Controlling Flavohemoglobin Toxicity

Authors

Ryan M. Singh, University of Nebraska Medical CenterFollow
Sujata S. Chaudhari, University of Nebraska Medical CenterFollow
Sasmita Panda, University of Nebraska Medical CenterFollow
Elizabeth H. Hutfless, University of Nebraska Medical Center
Cortney E. Heim, University of Nebraska Medical Center
Dhananjay Shinde, University of Nebraska Medical CenterFollow
Abdulelah A. Alqarzaee, University of Nebraska Medical Center
Margaret F. Sladek, University of Nebraska Medical CenterFollow
Vineet Kumar, University of Nebraska Medical Center
Matthew C. Zimmerman, University of Nebraska Medical CenterFollow
Paul D. Fey, University of Nebraska Medical CenterFollow
Tammy Kielian, University of Nebraska Medical CenterFollow
Vinai Chittezham Thomas, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Redox Biology

Publication Date

2023

Volume

67

Abstract

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 (O₂^•-) from its heme prosthetic group which impedes growth. To limit Hmp toxicity, nitrite (NO₂^-) 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.

MeSH Headings

Bacterial Proteins, Oxidative Stress, Nitric Oxide Synthase, Oxidation-Reduction, Nitric Oxide

DOI Link

10.1016/j.redox.2023.102935

ISSN

2213-2317

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Singh, Ryan M.; Chaudhari, Sujata S.; Panda, Sasmita; Hutfless, Elizabeth H.; Heim, Cortney E.; Shinde, Dhananjay; Alqarzaee, Abdulelah A.; Sladek, Margaret F.; Kumar, Vineet; Zimmerman, Matthew C.; Fey, Paul D.; Kielian, Tammy; and Chittezham Thomas, Vinai, "A Critical Role for Staphylococcal Nitric Oxide Synthase in Controlling Flavohemoglobin Toxicity" (2023). Journal Articles: Cellular & Integrative Physiology. 51.
https://digitalcommons.unmc.edu/com_cell_articles/51