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表皮葡萄球菌新型大环内酯-链阳菌素B耐药决定子的鉴定与分子克隆

Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis.

作者信息

Ross J I, Farrell A M, Eady E A, Cove J H, Cunliffe W J

机构信息

Department of Microbiology, University of Leeds, UK.

出版信息

J Antimicrob Chemother. 1989 Dec;24(6):851-62. doi: 10.1093/jac/24.6.851.

DOI:10.1093/jac/24.6.851
PMID:2559912
Abstract

A total of 110 staphylococcal isolates from human skin were found to express a novel type of erythromycin resistance. The bacteria were resistant to 14-membered ring macrolides (MIC 32-128 mg/l) but were sensitive to 16-membered ring macrolides and lincosamides. Resistance to type B streptogramins was inducible by erythromycin. A similar phenotype, designated MS resistance, was previously described in clinical isolates of coagulase-negative staphylococci from the USA. In the UK, MS resistance is widely distributed in coagulase-negative staphylococci but was not detected in 100 erythromycin resistant clinical isolates of Staphylococcus aureus. Tests for susceptibility to a further 16 antibiotics failed to reveal any other selectable marker associated with the MS phenotype. Plasmid pattern analysis of 48 MS isolates showed considerable variability between strains and no common locus for the resistance determinant. In one strain of S. epidermidis co-resistance to tetracycline, penicillin and erythromycin (MS) was associated with a 31.5 kb plasmid, pUL5050 which replicated and expressed all three resistances when transformed into S. aureus RN4220. The MS resistance determinant was localised to a 1.9 kb fragment which was cloned on to the high-copy-number vector, pSK265. A constitutive mutant of S. aureus RN4220 containing the 1.9 kb fragment remained sensitive to clindamycin. This observation, together with the concentration-dependent induction (optimum 5 mg/l of erythromycin) of virginiamycin S resistance suggests that the MS phenotype is not due to altered expression of MLS resistance determinants (erm genes) but probably occurs via a different mechanism.

摘要

从人皮肤分离出的110株葡萄球菌被发现表达一种新型的红霉素耐药性。这些细菌对14元环大环内酯类抗生素耐药(MIC为32 - 128mg/L),但对16元环大环内酯类抗生素和林可酰胺类敏感。对B型链阳菌素的耐药性可被红霉素诱导。一种类似的表型,称为MS耐药,先前在美国凝固酶阴性葡萄球菌的临床分离株中被描述过。在英国,MS耐药在凝固酶阴性葡萄球菌中广泛分布,但在100株耐红霉素的金黄色葡萄球菌临床分离株中未检测到。对另外16种抗生素的敏感性测试未能揭示与MS表型相关的任何其他可选择标记。对48株MS分离株的质粒图谱分析显示菌株间存在很大差异,且耐药决定簇没有共同位点。在一株表皮葡萄球菌中,对四环素、青霉素和红霉素的共耐药性(MS)与一个31.5kb的质粒pUL5050相关,当将其转化到金黄色葡萄球菌RN4220中时,该质粒可复制并表达所有三种耐药性。MS耐药决定簇定位于一个1.9kb的片段,该片段被克隆到高拷贝数载体pSK265上。含有1.9kb片段的金黄色葡萄球菌RN4220组成型突变体对克林霉素仍敏感。这一观察结果,连同对维吉尼亚霉素S耐药性的浓度依赖性诱导(最佳红霉素浓度为5mg/L)表明,MS表型不是由于MLS耐药决定簇(erm基因)表达改变所致,而可能是通过不同机制发生的。

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