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高频率存在于亚临床牛乳腺炎分离株中的高突变性金黄色葡萄球菌菌株与抗生素耐药性的发展有关。

Hypermutable Staphylococcus aureus strains present at high frequency in subclinical bovine mastitis isolates are associated with the development of antibiotic resistance.

机构信息

Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.

出版信息

Vet Microbiol. 2013 Aug 30;165(3-4):410-5. doi: 10.1016/j.vetmic.2013.04.009. Epub 2013 Apr 12.

Abstract

Hypermutable bacterial strains with greatly elevated spontaneous mutation rates have been described at high frequencies in various clinically important species, particularly in cystic fibrosis (CF) patients. It has been suggested that such strains can play a major role in the development of chronic respiratory infections. Nevertheless, little information is available regarding the potential association between hypermutation and other chronic infection settings. Here, we investigated the mutation frequencies of 261 Staphylococcus aureus isolates from bovine mastitis cases. The comparative analysis revealed that the subclinical mastitis (SM) isolates harbored significantly more hypermutators than the clinical mastitis (CM) isolates (26/141 versus 0/120, P<0.001, Fisher's exact test). Analysis of mutS and mutL genes, which are major components of the methyl mismatch repair (MMR) system, revealed that 13 of the 14 genetically unrelated hypermutators showed alterations in their deduced MutS and/or MutL amino acid sequences. The hypermutators were much more frequently found to be resistant to all of the 7 antibiotics tested (except sulfafurazole) than the nonmutators. Moreover, the proportion of hypermutators harboring multi-drug resistance was significantly higher than that of the nonmutators as well (P<0.001). Taken together, this work provides evidence that hypermutability plays an important role in antibiotic resistance development during long-term persistence of S. aureus, and reveals that the link between hypermutation and chronic infections appears not to be restricted to respiratory infections alone.

摘要

高突变率的易变细菌株在各种临床重要物种中,特别是在囊性纤维化(CF)患者中被频繁描述。有人认为,这种菌株可以在慢性呼吸道感染的发展中发挥重要作用。然而,关于高突变与其他慢性感染环境之间的潜在关联的信息很少。在这里,我们调查了 261 株来自奶牛乳腺炎病例的金黄色葡萄球菌分离株的突变频率。比较分析显示,亚临床乳腺炎(SM)分离株比临床乳腺炎(CM)分离株携带更多的高突变体(26/141 比 0/120,P<0.001,Fisher 精确检验)。对 mutS 和 mutL 基因的分析,它们是甲基错配修复(MMR)系统的主要组成部分,揭示了 14 个遗传上无关的高突变体中的 13 个在其推断的 MutS 和/或 MutL 氨基酸序列中发生了改变。高突变体比非突变体更频繁地对所有 7 种测试的抗生素(除了磺胺嘧啶)产生耐药性。此外,携带多药耐药性的高突变体的比例也明显高于非突变体(P<0.001)。总之,这项工作提供了证据表明,高突变性在金黄色葡萄球菌长期持续存在期间对抗生素耐药性的发展起着重要作用,并表明高突变与慢性感染之间的联系似乎不仅限于呼吸道感染。

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