Department of Veterinary Medicine, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Department of Veterinary Medicine, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Microb Pathog. 2024 Nov;196:106961. doi: 10.1016/j.micpath.2024.106961. Epub 2024 Sep 21.
Antimicrobial-resistant (AMR) Staphylococcus aureus (S. aureus) strains have attained global attention due to their life-threatening zoonotic nature. Being a member of ESKAPE group, S. aureus has an ability to escape the biocidal action of antimicrobial drugs. The current study investigated the prevalence and molecular characterization of methicillin-resistant S. aureus (MRSA), β-lactam-resistant S. aureus (BRSA), aminoglycoside-resistant S. aureus (ARSA), tetracycline-resistant S. aureus (TRSA), and fluoroquinolones-resistant S. aureus (FRSA) associated with goat subclinical mastitis (SCM). Furthermore, the antimicrobial resistance and susceptibility profile of various antibiotics and non-antibiotics (NSAIDs, nisin, N-acetylcysteine, vitamin-C) along with their possible role in modulating the antibiotic resistance of MDR isolates was also investigated. A total of 768 goat milk samples were subjected to California mastitis test for SCM followed by bacteriological and molecular characterization of S. aureus. Moreover, in-vitro susceptibility of resistant antibiotics, non-antibiotics, and their combination against MDR S. aureus were conducted through well diffusion and broth microdilution assays. The results depicted that 55.47 % and 26.82 % of milk samples were positive for SCM and S. aureus, respectively. The molecular assay confirmed 35.92 % of isolates as MRSA, 45.63 % as BRSA, 50.49 % as ARSA, and 32.52 % but no isolate was confirmed as FRSA on molecular basis. The multidrug resistance was observed in 62.13 % and 47.09 % isolates, respectively. Molecular characterized MDR S. aureus revealed high homology of study isolates with the isolates of neighboring countries like India, Korea, Iran, and China. Antimicrobial susceptibility trials on well diffusion assay showed higher efficacy of different non-antibiotics with resistant antibiotics as penicillin with ketoprofen and gentamicin with flunixin meglumine while oxytetracycline with N-acetylcystiene. The synergy testing by checkerboard assay revealed synergistic activity of penicillin with ketoprofen, gentamicin with flunixin meglumine, and oxytetracycline with N-acetylcysteine. The current study highlighted the emergence and spread of AMR S. aureus strains from goat SCM and provided insights into possible drug repurposing of various non-antibiotics to modulate the multidrug resistance of S. aureus which will be helpful in devising the therapeutic options and control measures for this pathogen.
耐抗生素（AMR）金黄色葡萄球菌（S. aureus）菌株因其具有威胁生命的人畜共患病性质而受到全球关注。金黄色葡萄球菌作为 ESKAPE 群体的一员，具有逃避抗生素药物杀菌作用的能力。本研究调查了与山羊亚临床乳腺炎（SCM）相关的耐甲氧西林金黄色葡萄球菌（MRSA）、β-内酰胺类耐药金黄色葡萄球菌（BRSA）、氨基糖苷类耐药金黄色葡萄球菌（ARSA）、四环素类耐药金黄色葡萄球菌（TRSA）和氟喹诺酮类耐药金黄色葡萄球菌（FRSA）的流行情况和分子特征。此外，还研究了各种抗生素和非抗生素（NSAIDs、乳链菌肽、N-乙酰半胱氨酸、维生素 C）的抗生素耐药性和敏感性，并研究了它们在调节多药耐药（MDR）分离株抗生素耐药性方面的可能作用。对 768 份山羊奶样本进行加利福尼亚乳腺炎测试以检测 SCM，然后对金黄色葡萄球菌进行细菌学和分子特征分析。此外，通过平板扩散和肉汤微量稀释法对耐药抗生素、非抗生素及其组合对 MDR 金黄色葡萄球菌的体外敏感性进行了研究。结果表明，55.47%和 26.82%的奶样分别为 SCM 和金黄色葡萄球菌阳性。分子检测证实，35.92%的分离株为 MRSA，45.63%为 BRSA，50.49%为 ARSA，32.52%但没有分离株在分子基础上确认为 FRSA。62.13%和 47.09%的分离株分别表现出多药耐药性。分子特征分析的 MDR 金黄色葡萄球菌显示，研究分离株与印度、韩国、伊朗和中国等邻国的分离株具有高度同源性。平板扩散试验的抗生素敏感性试验显示，不同非抗生素与耐药抗生素（如青霉素与酮洛芬和庆大霉素与氟尼辛葡甲胺）联合使用的效果更好，而与 N-乙酰半胱氨酸联合使用的多西环素效果较差。棋盘试验的协同作用测试显示，青霉素与酮洛芬、庆大霉素与氟尼辛葡甲胺以及多西环素与 N-乙酰半胱氨酸具有协同活性。本研究强调了耐抗生素金黄色葡萄球菌从山羊 SCM 中出现和传播的情况，并提供了有关各种非抗生素药物重新利用以调节金黄色葡萄球菌的多药耐药性的信息，这将有助于制定针对该病原体的治疗选择和控制措施。
