Noguchi Norihisa
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
Yakugaku Zasshi. 2021;141(2):235-244. doi: 10.1248/yakushi.20-00225.
Antimicrobial resistance (AMR) is a serious problem worldwide. We searched for the AMR determinants of various bacteria isolated from clinical settings and studied their resistance mechanisms and molecular epidemiology. This review focuses on the AMR of Staphylococcus aureus, a major gram-positive pathogen, which has the ability to acquire resistance to antimicrobials. The resistance factors of S. aureus are frequently found on mobile elements, including plasmids and transposons. We determined the complete DNA sequence of the tetracycline-resistance plasmid and found that the inducible expression of tetK in S. aureus was regulated by a post-transcriptional attenuation mechanism. Furthermore, outbreaks of methicillin-resistant S. aureus (MRSA) in hospitals and communities have led us to study infection controls, including the antiseptic susceptibility evaluation and molecular epidemiology of MRSA. Various antiseptic resistance determinants, such as qacA/B and smr, were identified on plasmids and characterized. We demonstrated that the plasmid-mediated efflux pump QacB variant QacIII confers fluoroquinolone efflux ability to S. aureus. Studies on MRSA epidemiology had shown that community-acquired MRSA (CA-MRSA) was disseminated into hospitals and that an increased use of alcohol-based rubs could reduce the incidence of MRSA infections in such institutions. Additionally, the study of CA-MRSA collected from communities and hospitals showed an increase in Panton-Valentine leucocidin (PVL)-positive CA-MRSA, causing severe skin and soft tissue infections. Moreover, various PVL-positive CA-MRSA clones have disseminated in Japan, whereas the USA300 LV/J clone evolved in that country. Our study provides important information regarding MRSA infection control.
抗菌药物耐药性(AMR)是一个全球性的严重问题。我们寻找了从临床环境中分离出的各种细菌的AMR决定因素,并研究了它们的耐药机制和分子流行病学。本综述重点关注金黄色葡萄球菌的AMR,金黄色葡萄球菌是一种主要的革兰氏阳性病原体,具有获得抗菌药物耐药性的能力。金黄色葡萄球菌的耐药因子经常出现在包括质粒和转座子在内的可移动元件上。我们确定了四环素耐药质粒的完整DNA序列,发现金黄色葡萄球菌中tetK的诱导表达受转录后衰减机制调控。此外,医院和社区中耐甲氧西林金黄色葡萄球菌(MRSA)的暴发促使我们研究感染控制措施,包括MRSA的防腐剂敏感性评估和分子流行病学。在质粒上鉴定并表征了各种防腐剂耐药决定因素,如qacA/B和smr。我们证明了质粒介导的外排泵QacB变体QacIII赋予金黄色葡萄球菌氟喹诺酮外排能力。对MRSA流行病学的研究表明,社区获得性MRSA(CA-MRSA)已传播到医院,增加使用酒精擦手液可降低此类机构中MRSA感染的发生率。此外,对从社区和医院收集的CA-MRSA的研究表明,产Panton-Valentine杀白细胞素(PVL)的CA-MRSA有所增加,可导致严重的皮肤和软组织感染。此外,各种PVL阳性CA-MRSA克隆已在日本传播,而USA300 LV/J克隆则在该国进化。我们的研究提供了有关MRSA感染控制的重要信息。