Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene.
Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene.
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DOI：
10.1093/jac/dkt418
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Holmes MA
中科院分区：
文献类型：
--
作者：
Ba X;Harrison EM;Edwards GF;Holden MT;Larsen AR;Petersen A;Skov RL;Peacock SJ;Parkhill J;Paterson GK;Holmes MA
耐甲氧西林金黄色葡萄球菌（MRSA）是一个重要的全球卫生问题。MRSA对β-内酰胺类抗生素的耐药性是由mecA或mecC基因介导的，这些基因编码对β-内酰胺类抗生素具有低亲和力的替代青霉素结合蛋白（PBP） 2a。mec基因或PBP2a的检测被认为是MRSA诊断的金标准。我们鉴定了4株缺乏mecA或mecC基因的MRSA分离株，但仍对铅笔酶耐药β-内酰胺类抗生素具有表型抗性。通过全基因组测序和一系列表型分析对4株人金黄色葡萄球菌分离株进行了研究。我们在耐药菌株中发现了内源性PBPs 1、2和3中存在的一些氨基酸取代，但在密切相关的敏感菌株中却没有，这可能是耐药的基础。特别令人感兴趣的是PBPs 1、2和3中三个相同的氨基酸替换，它们独立发生在至少两个独立的多位点序列类型的分离物中。在两个不同序列类型的两个分离株中，PBP1的同一氨基酸也存在两个不同的非保守取代。这项工作表明，单纯使用分子方法可能会误诊表型耐药的MRSA，并提供了MRSA β-内酰胺耐药的替代机制的证据，这可能需要诊断实验室考虑。
Methicillin-resistant Staphylococcus aureus (MRSA) is an important global health problem. MRSA resistance to β-lactam antibiotics is mediated by the mecA or mecC genes, which encode an alternative penicillin-binding protein (PBP) 2a that has a low affinity to β-lactam antibiotics. Detection of mec genes or PBP2a is regarded as the gold standard for the diagnosis of MRSA. We identified four MRSA isolates that lacked mecA or mecC genes, but were still phenotypically resistant to pencillinase-resistant β-lactam antibiotics. The four human S. aureus isolates were investigated by whole genome sequencing and a range of phenotypic assays. We identified a number of amino acid substitutions present in the endogenous PBPs 1, 2 and 3 that were found in the resistant isolates but were absent in closely related susceptible isolates and which may be the basis of resistance. Of particular interest are three identical amino acid substitutions in PBPs 1, 2 and 3, occurring independently in isolates from at least two separate multilocus sequence types. Two different non-conservative substitutions were also present in the same amino acid of PBP1 in two isolates from two different sequence types. This work suggests that phenotypically resistant MRSA could be misdiagnosed using molecular methods alone and provides evidence of alternative mechanisms for β-lactam resistance in MRSA that may need to be considered by diagnostic laboratories.
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影响因子：
56.3
作者：
Garcia-Alvarez, Laura;Holden, Matthew T. G.;Lindsay, Heather;Webb, Cerian R.;Brown, Derek F. J.;Curran, Martin D.;Walpole, Enid;Brooks, Karen;Pickard, Derek J.;Teale, Christopher;Parkhill, Julian;Bentley, Stephen D.;Edwards, Giles F.;Girvan, E. Kirsty;Kearns, Angela M.;Pichon, Bruno;Hill, Robert L. R.;Larsen, Anders Rhod;Skov, Robert L.;Peacock, Sharon J.;Maskell, Duncan J.;Holmes, Mark A.
通讯作者：
Holmes, Mark A.
影响因子：
6.4
作者：
CHAMBERS, HF;SACHDEVA, M
通讯作者：
SACHDEVA, M
影响因子：
4.8
作者：
Fuda, C;Suvorov, M;Mobashery, S
通讯作者：
Mobashery, S
影响因子：
4.9
作者：
HACKBARTH, CJ;KOCAGOZ, T;CHAMBERS, HF
通讯作者：
CHAMBERS, HF
影响因子：
3.3
作者：
Gál, Z;Kovács, P;Szabó, I
通讯作者：
Szabó, I