猪源喹诺酮类耐药沙门氏菌产生机制与适应性研究

Salmonella infection is one of the most common foodborne bacterial diseases, and is often associated with the consumption of eggs, pork and chicken meat. Treatment failure in Salmonella infection is now often caused by the emergence of resistance to clinically important antimicrobials such as quinolones. In addition, the obviously increasing trend in the detection rates of quinolone-resistant Salmonella from pigs poses a great threat to the human healthy and public safety. What causes the rapidly increase in the Salmonella resistance? How is the Salmonella resistance disseminated? How much hazard to the human and / or animal health has the Salmonella resistance caused? To answer these questions, the prevalence and distribution of quinolone-resistant Salmonella from pigs will be investigated. Based on the comprehensive data acquired from the drug-pathogen-host point of view, the emergence of resistance, transmission mechanism, fitness and pathogenesis of quinolone-resistant Salmonella from pigs will be demonstrated. It is expected that the findings of this project will help us reveal the contributing factors leading to the rapid emergence of quinolone-resistant Salmonella from pigs, and the characteristics of the hazards to the human and / or animal health caused by quionolone-resistant Salmonella. The results from this project will provide important information for the strategy design of the prophylaxis and treatment of the antimicrobial resistance in bacteria of animal origin.

沙门氏菌感染是报道最多的食源性细菌病之一，并且常常与食用鸡蛋、猪肉和禽肉有关。沙门氏菌对喹诺酮类临床常用抗菌药物耐药导致动物发病后难于治疗。此外，猪源沙门氏菌喹诺酮类耐药株检出率呈明显上升趋势，给养殖业的健康发展和公共卫生带来极大威胁。什么原因导致耐药株数量迅速升高？耐药性怎样传播扩散，危害程度如何？针对以上问题，本课题拟从“药物-病原-机体”互作层面，通过调查获得猪源喹诺酮类耐药沙门氏菌的分布与流行特征基础上，开展喹诺酮类耐药沙门氏菌的产生与传播机制、适应性与致病性研究，旨在探明我国猪源沙门氏菌喹诺酮类耐药株大量出现的原因，揭示其危害特征，为有效防治家畜细菌感染性疾病和动物源病原菌耐药性的风险评估提供科学依据。

食源性疾病是威胁公共安全最重要的因素之一，而沙门氏菌是一种广泛分布于自然界、人和动物肠道中常见的食源性致病菌。猪是沙门氏菌的第二大宿主，在猪只养殖过程中，沙门氏菌极易通过粪便、水、土壤、饲料和空气等传播给养殖人员，尤其是在集中规模化的养殖方式下，畜禽数目庞大，养殖空间狭小，加剧了传播风险。沙门氏菌对喹诺酮类临床常用抗菌药物耐药导致动物发病后难于治疗。此外，猪源沙门氏菌喹诺酮类耐药株检出率呈明显上升趋势，给养殖业的健康发展和公共卫生带来极大威胁。本课题针对新疆主要养猪场分离的沙门菌，通过琼脂稀释法获取菌株对临床常用抗菌药物的耐药信息，使用PCR检测PMQR基因、β-内酰胺酶和氨基糖苷类耐药基因，使用二代测序对多重耐药菌株的流行状况进行调查，应用高通量测序技术探究了外源多重耐药鼠伤寒沙门菌进入健康小鼠肠道后对其肠道菌群的影响，同时探索外源多耐沙门氏菌在健康小鼠肠道菌群中可能存在的耐药性传播机制。此外还对新疆不同动物来源的肠球菌与大肠杆菌的耐药性进行了调查。上述研究有助于阐明耐药菌株迅速产生和耐药基因扩散的原因，且对临床合理用药有一定的指导意义。