金黄色葡萄球菌喹奴普丁-达福普汀耐药新基因lsa(E)水平转移机制研究

金黄色葡萄球菌是医院及社区获得性感染的主要病原菌。2005年家畜相关耐甲氧西林金葡菌被广泛关注，该类菌株可以越过物种屏障，传播到人类，这一发现导致抗生素类动物促生长剂与临床抗生素交叉耐药问题日趋严重。喹奴普丁-达福普汀属于链阳菌素类新型抗生素，该药目前还未在我国上市。但本课题组前期研究发现，由于维吉霉素（同属链阳菌素类）在我国动物饲料添加剂中的使用，导致猪携带菌株对喹奴普丁-达福普汀具有高耐药率，而这种耐药现象似乎已经开始向医院波及。在我国北方，97%的猪耐药菌株携带一个新的耐药基因lsa(E), 该耐药基因可能从肠球菌水平转移而来。本研究欲对lsa(E)水平转移机制进行初步探讨。通过结合转移实验，评价lsa(E)在粪肠球菌与金黄色葡萄球菌间水平转移的可能性；利用噬菌体转导技术，评价lsa(E)在不同金葡菌克隆系间水平转移的可能性，为耐药菌株的预防控制策略和抗生素类促生剂的合理使用提供依据.

Staphylococcus aureus is an important pathogen that can cause a wide variety of hospital- and community-acquired infections. After 2005, livestock associated methicillin-resistant S. aureus (LA-MRSA) was more and more paid attention to. LA-MRSA can also go across the specices barrier to spread to human and even in hospital.This finding also cause cross-resistance to clinic antibiotics by growth promotor antibiotics in animals a matter of concern. Quinupristin/dalfopristin is a new streptogramin antibiotic with a spectrum of activity that includes Gram-positive pathogens, including those resistant to other classes of antimicrobial compounds. Until now this antibiotic wasn't market in China. Based on our previous research, a high resistance rate to quinupristin/dalfopristin was observed in animal isolates with the trend spreading to hospitals because vigimycin was widely used as a growth promotor in China. A new quinupristin/dalfopristin resistance gene lsa(E) was found in 97% resistance isolates with pig origin in northeast China. Lsa(E) maybe originated from enterococcus by horizon gene transfer. In this research work, horizon gene transfer of lsa(E) from enterococcus to different S.aureus lineages by conjugation and transfer of lsa(E) among different S.aureus lineages by phage transduction will be evaluated.This work will provide the theory basis for prevention and control of multiresistant S.aureus isolates and valid usage of growth promotor for animals in China.