Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Increased Antibiotic Resistance of Methicillin-Resistant Staphylococcus aureus USA300 Δpsm Mutants and a Complementation Study of Δpsm Mutants Using Synthetic Phenol-Soluble Modulins

  • Song, Hun-Suk (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Bhatia, Shashi Kant (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Choi, Tae-Rim (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Gurav, Ranjit (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Kim, Hyun Joong (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Lee, Sun Mi (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Park, Sol Lee (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Lee, Hye Soo (Department of Biological Engineering, College of Engineering, Konkuk University) ;
  • Joo, Hwang-Soo (Department of Biotechnology, College of Engineering, Duksung Women's University) ;
  • Kim, Wooseong (College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Seo, Seung-Oh (Department of Food Science and Nutrition, Catholic University of Korea) ;
  • Yang, Yung-Hun (Department of Biological Engineering, College of Engineering, Konkuk University)
  • Received : 2020.07.02
  • Accepted : 2020.10.05
  • Published : 2021.01.28
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Abstract

Phenol-soluble modulins (PSMs) are responsible for regulating biofilm formation, persister cell formation, pmtR expression, host cell lysis, and anti-bacterial effects. To determine the effect of psm deletion on methicillin-resistant Staphylococcus aureus, we investigated psm deletion mutants including Δpsmα, Δpsmβ, and Δpsmαβ. These mutants exhibited increased β-lactam antibiotic resistance to ampicillin and oxacillin that was shown to be caused by increased N-acetylmannosamine kinase (nanK) mRNA expression, which regulates persister cell formation, leading to changes in the pattern of phospholipid fatty acids resulting in increased anteiso-C15:0, and increased membrane hydrophobicity with the deletion of PSMs. When synthetic PSMs were applied to Δpsmα and Δpsmβ mutants, treatment of Δpsmα with PSMα1-4 and Δpsmβ with PSMβ1-2 restored the sensitivity to oxacillin and slightly reduced the biofilm formation. Addition of a single fragment showed that α1, α2, α3, and β2 had an inhibiting effect on biofilms in Δpsmα; however, β1 showed an enhancing effect on biofilms in Δpsmβ. This study demonstrates a possible reason for the increased antibiotic resistance in psm mutants and the effect of PSMs on biofilm formation.

Keywords

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