The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus

Megha Gulati; Jason M Thomas; Craig L Ennis; Aaron D Hernday; Mamta Rawat; Clarissa J Nobile

doi:10.1016/j.micpath.2024.106657

The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus

Microb Pathog. 2024 Apr 20:191:106657. doi: 10.1016/j.micpath.2024.106657. Online ahead of print.

Authors

Megha Gulati¹, Jason M Thomas², Craig L Ennis³, Aaron D Hernday⁴, Mamta Rawat⁵, Clarissa J Nobile⁶

Affiliations

¹ Department of Molecular and Cell Biology, University of California Merced, Merced, CA, USA.
² Department of Biology, California State University-Fresno, Fresno, CA, USA.
³ Department of Molecular and Cell Biology, University of California Merced, Merced, CA, USA; Quantitative and Systems Biology Graduate Program, University of California, Merced, CA, USA.
⁴ Department of Molecular and Cell Biology, University of California Merced, Merced, CA, USA; Health Sciences Research Institute, University of California, Merced, CA, USA.
⁵ Department of Biology, California State University-Fresno, Fresno, CA, USA. Electronic address: mrawat@csufresno.edu.
⁶ Department of Molecular and Cell Biology, University of California Merced, Merced, CA, USA; Health Sciences Research Institute, University of California, Merced, CA, USA. Electronic address: cnobile@ucmerced.edu.

PMID: 38649100
DOI: 10.1016/j.micpath.2024.106657

Abstract

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus.