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揭示奶牛乳腺炎病原菌多药耐药的复杂机制:对抗菌药物耐药基因、生物膜动态和外排系统的深入了解。

Unravelling the complex mechanisms of multidrug resistance in bovine mastitis pathogens: Insights into antimicrobial resistance genes, biofilm dynamics, and efflux systems.

机构信息

Department of Veterinary Epidemiology and Preventive Medicine, College of Veterinary and Animal Sciences, Pookode, Wayanad, 673576, Kerala, India, Kerala Veterinary and Animal Sciences University.

Department of Veterinary Epidemiology and Preventive Medicine, College of Veterinary and Animal Sciences, Pookode, Wayanad, 673576, Kerala, India, Kerala Veterinary and Animal Sciences University.

出版信息

Microb Pathog. 2024 Oct;195:106902. doi: 10.1016/j.micpath.2024.106902. Epub 2024 Aug 31.

DOI:10.1016/j.micpath.2024.106902
PMID:39218374
Abstract

Mastitis remains a paramount economic threat to dairy livestock, with antibiotic resistance severely compromising treatment efficacy. This study provides an in-depth investigation into the multidrug resistance (MDR) mechanisms in bacterial isolates from bovine mastitis, emphasizing the roles of antimicrobial resistance genes (ARGs), biofilm formation, and active efflux systems. A total of 162 Staphylococci, eight Escherichia coli, and seven Klebsiella spp. isolates were obtained from 215 milk samples of clinical and subclinical mastitis cases. Antibiotic susceptibility testing identified Twenty Staphylococci (12.35 %), six E. coli (75 %) and seven Klebsiella (100 %) identified as MDR displaying significant resistance to β-lactams and tetracyclines The Multiple Antibiotic Resistance (MAR) index of these isolates ranged from 0.375 to 1.0, highlighting extensive resistance. Notably, 29 of the 33 MDR isolates produced biofilms on Congo red agar, while all exhibited biofilm formation in the Microtitre Plate assay. Critical ARGs (blaZ, blaTEM, blaCTX-M, tetM, tetA, tetB, tetC, strA/B, aadA) and efflux pump genes (acrB, acrE, acrF, emrB, norB) regulating active efflux were identified. This pioneering study elucidates the synergistic contribution of ARGs, biofilm production, and efflux pump activity to MDR in bovine mastitis pathogens. To our knowledge, this comprehensive study is the first of its kind, offering novel insights into the complex resistance mechanisms. The findings underscore the imperative need for advanced antibiotic stewardship and strategic interventions in dairy farming to curb the rise of antibiotic-resistant infections, thereby protecting both animal and public health.

摘要

乳腺炎仍然是奶牛养殖业的主要经济威胁,抗生素耐药性严重影响了治疗效果。本研究深入探讨了奶牛乳腺炎分离菌的多药耐药(MDR)机制,强调了抗菌药物耐药基因(ARGs)、生物膜形成和主动外排系统的作用。从 215 份临床和亚临床乳腺炎病例的牛奶样本中获得了 162 株葡萄球菌、8 株大肠杆菌和 7 株克雷伯氏菌分离株。抗生素药敏试验鉴定出 20 株葡萄球菌(12.35%)、6 株大肠杆菌(75%)和 7 株克雷伯氏菌(100%)为 MDR,对β-内酰胺类和四环素类药物表现出显著耐药性。这些分离株的多重抗生素耐药(MAR)指数为 0.375 至 1.0,表明存在广泛耐药性。值得注意的是,33 株 MDR 分离株中有 29 株在刚果红琼脂上产生生物膜,而所有分离株在微量滴定板试验中均表现出生物膜形成。关键的 ARGs(blaZ、blaTEM、blaCTX-M、tetM、tetA、tetB、tetC、strA/B、aadA)和调节主动外排的外排泵基因(acrB、acrE、acrF、emrB、norB)被鉴定出来。这项开创性的研究阐明了 ARGs、生物膜产生和外排泵活性对奶牛乳腺炎病原体 MDR 的协同贡献。据我们所知,这是此类研究中的首例,为复杂的耐药机制提供了新的见解。这些发现强调了在奶牛养殖中加强抗生素管理和采取战略干预措施的必要性,以遏制抗生素耐药性感染的上升,从而保护动物和公共健康。

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