Study of SarA by DNA Affinity Capture Assay (DACA) Employing Three Promoters of Key Virulence and Resistance Genes in Methicillin-Resistant Staphylococcus aureus

Byungchan Kim, Hong Ju Lee, Sung Hyun Jo, Min Gyu Kim, Yeonhee Lee, Wonsik Lee, Wooseong Kim, Hwang Soo Joo, Yun Gon Kim, Jae Seok Kim, Yung Hun Yang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), one of the most well-known human pathogens, houses many virulence factors and regulatory proteins that confer resistance to diverse antibiotics. Although they have been investigated intensively, the correlations among virulence factors, regulatory proteins and antibiotic resistance are still elusive. We aimed to identify the most significant global MRSA regulator by concurrently analyzing protein-binding and several promoters under same conditions and at the same time point. DNA affinity capture assay (DACA) was performed with the promoters of mecA, sarA, and sarR, all of which significantly impact survival of MRSA. Here, we show that SarA protein binds to all three promoters. Consistent with the previous reports, ΔsarA mutant exhibited weakened antibiotic resistance to oxacillin and reduced biofilm formation. Additionally, production and activity of many virulence factors such as phenol-soluble modulins (PSM), α-hemolysin, motility, staphyloxanthin, and other related proteins were decreased. Comparing the sequence of SarA with that of clinical strains of various lineages showed that all sequences were highly conserved, in contrast to that observed for AgrA, another major regulator of virulence and resistance in MRSA. We have demonstrated that SarA regulates antibiotic resistance and the expression of various virulence factors. Our results warrant that SarA could be a leading target for developing therapeutic agents against MRSA infections.

Original languageEnglish
Article number1714
JournalAntibiotics
Volume11
Issue number12
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This study was supported by the Research Program to solve social issues with the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT [grant number 2017M3A9E4077234].

Publisher Copyright:
© 2022 by the authors.

Keywords

  • clinical strain
  • DACA
  • MRSA
  • sarA
  • virulence factors

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