Shibata Hirofumi, Shirakata Chikako, Kawasaki Hiromi, Sato Yoichi, Kuwahara Tomomi, Ohnishi Yoshinari, Arakaki Naokatu, Higuti Tomihiko
Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Biol Pharm Bull. 2003 Oct;26(10):1478-83. doi: 10.1248/bpb.26.1478.
Flavone and its derivatives had very weak antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus, but dramatically intensified MRSA's susceptibility to beta-lactams. We named these compounds "ILSMR (intensifier of beta-lactam-susceptibility in MRSA)." We also found discrepancies among MRSA strains in their responses to flavone; some strains showed phenotypic susceptibility to methicillin while others showed phenotypic resistance to it. To understand the mechanism underlying this discrepancy, we characterized 20 MRSA strains in detail, analyzed their conventional and molecular typings, and examined each strain's resistance to beta-lactams, with COL serving as a reference. Neither SCCmec typing nor coagulase typing explained the diverse effects of flavone on the beta-lactam MICs of these strains. Likewise, changes in pulsed-field gel electrophoresis (PFGE) type were not associated with the profiles of ILSMR effects. However, the present observations suggest that the ILSMR effects on MRSA is strain-specific, and that this effect depends on an as-yet unknown mechanism that is essential for the expression of the phenotype conferring beta-lactam resistance to MRSA strains, independently of an interaction with the mecA-encoded penicillin-binding protein 2a or with the beta-lactamase.
黄酮及其衍生物对耐甲氧西林金黄色葡萄球菌（MRSA）和甲氧西林敏感金黄色葡萄球菌的抗菌作用非常微弱，但能显著增强MRSA对β-内酰胺类药物的敏感性。我们将这些化合物命名为“ILSMR（MRSA中β-内酰胺敏感性增强剂）”。我们还发现不同MRSA菌株对黄酮的反应存在差异；一些菌株表现出对甲氧西林的表型敏感性，而另一些则表现出表型耐药性。为了解这种差异背后的机制，我们详细鉴定了20株MRSA菌株，分析了它们的传统分型和分子分型，并以COL为参照检测了各菌株对β-内酰胺类药物的耐药性。SCCmec分型和凝固酶分型均无法解释黄酮对这些菌株β-内酰胺最低抑菌浓度（MIC）的不同影响。同样，脉冲场凝胶电泳（PFGE）类型的变化与ILSMR效应的模式无关。然而，目前的观察结果表明，ILSMR对MRSA的作用具有菌株特异性，且这种作用取决于一种尚未明确的机制，该机制对于赋予MRSA菌株β-内酰胺耐药性的表型表达至关重要，与mecA编码的青霉素结合蛋白2a或β-内酰胺酶的相互作用无关。
