KMID : 0545120210310010115
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Journal of Microbiology and Biotechnology 2021 Volume.31 No. 1 p.115 ~ p.122
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Increased Antibiotic Resistance of Methicillin-Resistant Staphylococcus aureus USA300 ¥Äpsm Mutants and a Complementation Study of ¥Äpsm Mutants Using Synthetic Phenol-Soluble Modulins
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Song Hun-Suk
Bhatia Shashi Kant Choi Tae-Rim Gurav Ranjit Kim Hyun-Joong Lee Sun-Mi Park Sol-Lee Lee Hye-Soo Joo Hwang-Soo Kim Woo-Seong Seo Seung-Oh Yang Yung-Hun
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Abstract
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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 ¥Äpsm¥á, ¥Äpsm¥â, and ¥Äpsm¥á¥â;. These mutants exhibited increased ¥â-lactam antibiotic resistance to ampicillin and oxacillin that was shown to be caused by increased Nacetylmannosamine 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 ¥Äpsm¥á and ¥Äpsm¥â mutants, treatment of ¥Äpsm¥á with PSM¥á1-4 and ¥Äpsm¥â with PSM¥â1-2 restored the sensitivity to oxacillin and slightly reduced the biofilm formation. Addition of a single fragment showed that ¥á1, ¥á2, ¥á3, and ¥â2 had an inhibiting effect on biofilms in ¥Äpsm¥á; however, ¥â1 showed an enhancing effect on biofilms in ¥Äpsm¥â. This study demonstrates a possible reason for the increased antibiotic resistance in psm mutants and the effect of PSMs on biofilm formation.
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KEYWORD
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MRSA, phenol-soluble modulins, ¥â-lactam antibiotic, biofilm, fatty acid, persister cell
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