重庆地区耐甲氧西林金黄色葡萄球菌主要流行克隆更替的机制研究

Mechanisms in replacement of major methicillin-resistant Staphylococcus aureus epidemic clones in Chongqing

目的探讨重庆地区耐甲氧西林金黄色葡萄球菌菌株ST239-MRSA-Ⅲ-t030替代ST239-MRSA-Ⅲ-t037克隆的机制。方法选择重庆地区分离的ST239-MRSA-Ⅲ-t030和ST239-MRSA-Ⅲ-t037临床株,检测各菌株的生长曲线,观察菌落形态,分析菌株的药物敏感谱;再通过体外、体内竞争实验和交叉抑制实验深入探讨ST239-MRSA-Ⅲ-t030替代ST239-MRSA-Ⅲ-t037的机制。结果 ST239-MRSA-Ⅲ-t030菌株较ST239-MRSA-Ⅲ-t037有更短的生长迟缓期,后者在固体培养基上生长的菌落相对较小,且都对复方新诺明耐药,对利福平敏感,这与ST239-MRSA-Ⅲ-t030菌株不同(大多数对复方新诺明敏感,对利福平都耐药)。ST239-MRSA-Ⅲ-t030菌株在体外和体内都表现出比ST239-MRSA-Ⅲ-t037菌株更强的生存竞争优势,但两克隆的菌株间并不存在明显的交叉抑制现象。结论 ST239-MRSA-Ⅲ-t030克隆的生存竞争优势和独特的耐药表型可能是其成功替代ST239-MRSA-Ⅲ-t037而成为第一流行克隆的原因。

Objective To explore the mechanisms underlying the replacement of methicillin-resistant Staphylococcus aureus （MRSA） straim ST239-MRSA-Ⅲ-t037 by ST239-MRSA-Ⅲ-t030 in Chongqing, China. Methods Eight ST239-MRSA-Ⅲ-t030 and ST239-MRSA-Ⅲ-t037 isolates collected from Chongqing were divided into four t030/t037 pairs. The independent growth rates of all isolates were then determined. The competitive growth rates of the bacterial pairs were detected in vitro and in vivo, and cross inhibition assays were also performed. Results The ST239-MRSA-III-t030 isolates were rifampicin-resistant, whereas the ST239- MRSA-Ⅲ-t037 strains were all rifampicin-sensitive and trimethoprim/sulfamethoxazole-resistant. The ST239- MRSA-III-t030 strains had shorter lag phases than the ST239-MRSA-Ⅲ-t037 isolates. The srr239-MRSA-Ⅲ- tO30 strains could out-compete their rivals in a competition assay in vitro as well as in a mouse model. No signif- icant cross-inhibition effect was observed between ST239-MRSA-Ⅲ-t030 and ST239-MRSA-Ⅲ-t037. The growth of ST239-MRSA-Ⅲ-t 4037 strains on the BHI nonselective plates had smaller colonies as compared to ST239-MRSA- re-to30 strains. Conclusion ST239-MRSA- lU-t030 replacing ST239-MRSA- re-to37 as the first predominant clone may result from its higher growth rate and the specific drug resistance profiles.