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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1476287

SarZ inhibits the hemolytic activity through regulation of phenol soluble modulins in Staphylococcus epidermidis

Provisionally accepted
Xiao Chen Xiao Chen 1Huiru Sun Huiru Sun 2Wei Wang Wei Wang 2Han Wang Han Wang 2Runan Tan Runan Tan 1Tao Zhu Tao Zhu 1*
  • 1 Department of Medical microbiology and Immunology, Wannan Medical College, Wuhu, China
  • 2 Department of Pharmacy, Wannan Medical College, Wuhu, China

The final, formatted version of the article will be published soon.

    Background: Staphylococcus epidermidis is an important conditionally pathogenic bacterium. SarZ, belonging to the SarA family protein, has been demonstrated in S. aureus to promote the expression of invasive virulence factors while inhibiting biofilm formation. However, the regulatory role of SarZ on S. epidermidis virulence is not completely understood.In this study, we successfully deleted the sarZ gene by allelic replacement in S. epidermidis. The sarZ mutant strain exhibited remarkably increased hemolytic activity and drastically impaired biofilm formation, suggesting that SarZ is key regulator of virulence in S. epidermidis. Through butanol extraction of the spent medium and HPLC-MS/MS analysis, production of phenol soluble modulins (PSMs) possessing cytolytic effect was found to be elevated significantly in the mutant. Subsequent qRT-PCR experiments demonstrated that expression of the psm genes, especially the -type, was upregulated dramatically in the mutant. Meanwhile, transcription of icaA gene responsible for biofilm formation was sharply diminished. The sarZ psm double mutant was further generated and displayed a significantly decreased hemolytic activity compared with the sarZ mutant EMSA assays implied that recombinant SarZ protein can directly bind to the promoter regions of the psm and ica operon. DNase I Footprinting assays further pinpointed two SarZ-binding sites on the indicated that SarZ is a regulator of psm operons promoter.Taken together, the results confirmed that SarZ is a pivotal regulator of virulence in S. epidermidis and might respectively regulate the hemolytic activity and biofilm formation mainly by directly controlling the transcription of psm genes, particularly the -type, and the ica operon.

    Keywords: Staphylococcus epidermidis, sarZ, Hemolysis, phenol-soluble modulins, Biofilm

    Received: 05 Aug 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Chen, Sun, Wang, Wang, Tan and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tao Zhu, Department of Medical microbiology and Immunology, Wannan Medical College, Wuhu, China

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