Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Infect Dis. Apr 26, 2022; 12(1): 20-32
Published online Apr 26, 2022. doi: 10.5495/wjcid.v12.i1.20
Mutations of the brpR and brpS genes affect biofilm formation in Staphylococcus aureus
Allison Zank, Lillian Schulte, Xavier Brandon, Lauren Carstensen, Amy Wescott, William R Schwan
Allison Zank, Lillian Schulte, Xavier Brandon, Lauren Carstensen, Amy Wescott, William R Schwan, Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, United States
Author contributions: Zank A, Wescott A, and Schwan WR designed the research study; Zank A, Schulte L, Brandon X, Carstensen L, Wescott A, and Schwan WR performed the research; Zank A, Brandon X, and Schwan WR contributed new plasmids; Zank A, and Schwan WR analyzed the data and wrote the manuscript; and all authors have read and approved the final manuscript.
Supported by National Science Foundation Graduate Research Program to Zank A, No. 0002016179620.
Institutional review board statement: No humans or samples from human were used in this study.
Institutional animal care and use committee statement: No animals were used in this study.
Conflict-of-interest statement: Schwan WR holds a composition of matter and use patent covering the SK-03-92 Lead compound.
Data sharing statement: The authors will share their data with whomever asks.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: William R Schwan, PhD, Professor, Department of Microbiology, University of Wisconsin-La Crosse, 1725 State St, La Crosse, WI 54601, United States.wschwan@uwlax.edu
Received: September 2, 2021
Peer-review started: September 2, 2021
First decision: November 22, 2021
Revised: December 3, 2021
Accepted: February 12, 2022
Article in press: February 12, 2022
Published online: April 26, 2022
Abstract
BACKGROUND

In the United States, Staphylococcus aureus (S. aureus) kills tens of thousands of individuals each year and the formation of a biofilm contributes to lethality. Biofilm-associated infections are hard to treat once the biofilm has formed. A new stilbene drug, labeled SK-03-92, was shown to kill S. aureus and affected transcription of two genes tied to a putative two-component system (TCS) we have named brpR (biofilm regulating protein regulator) and brpS (biofilm regulating protein sensor).

AIM

To determine if BrpR and BrpS regulate biofilm formation, brpR and brpS mutants were assessed using biofilm assays compared to wild-type S. aureus.

METHODS

A combination of biofilm and quantitative real-time-polymerase chain reaction assays were used. In addition, bioinformatic software tools were also utilized.

RESULTS

Significantly more biofilm was created in the brpR and brpS mutants vs wild-type cells. Quantitative real-time polymerase chain reactions showed the brpS mutant had differences in transcription of biofilm associated genes that were eight-fold higher for srtA, two-fold lower for lrgA, and 1.6-fold higher for cidA compared to wild-type. Bioinformatic analysis demonstrated that the S. aureus brpR/brpS TCS had homology to streptococcal late-stage competence proteins involved in cell-death, increased biofilm production, and the development of persister cells.

CONCLUSION

Our study suggests that brpR/brpS is a TCS that may repress S. aureus biofilm production and be linked to late-stage competence in S. aureus.

Keywords: Biofilm, Two-component system, Stilbene, Staphylococcus aureus, Late-stage competence, SK-03-92

Core Tip: Staphylococcus aureus is a primary cause of skin/soft tissue infections. In this study, we have shown that two previously uncharacterized genes, brpR and brpS, encode proteins that we believe comprise a two-component system that regulates biofilm formation in S. aureus.