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Novel single-nucleotide variations associated with vancomycin resistance in vancomycin-intermediate Staphylococcus aureus

机译:万古霉素中间型金黄色葡萄球菌中与万古霉素耐药相关的新型单核苷酸变异

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Prolonged vancomycin usage may cause methicillin-resistant Staphylococcus aureus to become vancomycin-intermediate S . aureus (VISA) and heterogeneous VISA (hVISA). Mechanisms of vancomycin resistance of VISA and hVISA are still unclear. In this study, analyses of nucleotide sequence variations in 30 vancomycin-sensitive S . aureus (VSSA), 41 hVISA and 16 VISA isolates revealed 29 single-nucleotide variations in 12 genes ( fmtC , graR , graS , htrA , mecA , pbp2 , pbp4 , srtA , tcaA , upps , vicK and vraR ) that are related to cell wall synthesis or the two-component system. Six of these 29 single-nucleotide variations were novel and resulted in the following amino acid changes: Q692E in FmtC; T278I, P306L and I311T in HtrA; and I63V and K101E in Upps. Since P306L and I311T in HtrA and I63V in Upps were present in the majority (76.7%–86.7%) of VSSA isolates, these three amino acid variations may not be associated with vancomycin resistance. The other three amino acid variations (T278I in HtrA, K101E in Upps and Q692E in FmtC) were present in the majority (87.5%–93.8%) of hVISA and VISA isolates, but only in a small number (22.9%–25.7%) of VSSA isolates, suggesting that they are associated with vancomycin resistance.
机译:万古霉素的长期使用可能导致耐甲氧西林的金黄色葡萄球菌成为万古霉素中间体。金黄色葡萄球菌(VISA)和异种VISA(hVISA)。 VISA和hVISA对万古霉素耐药的机制仍不清楚。在这项研究中,分析了30个对万古霉素敏感的S核苷酸序列的变异。金黄色葡萄球菌(VSSA),41种hVISA和16种VISA分离物揭示了与细胞相关的12个基因(fmtC,graR,graS,htrA,mecA,pbp2,pbp4,srtA,tcaA,upps,vicK和vraR)的29个单核苷酸变异壁合成或两组分系统。这29个单核苷酸变异中有6个是新颖的,并导致以下氨基酸变化:FmtC中的Q692E; HtrA中的T278I,P306L和I311T;以及Upps中的I63V和K101E。由于HtrA中的P306L和I311T和Upps中的I63V存在于大多数(76.7%–86.7%)VSSA分离物中,因此这三个氨基酸变异可能与万古霉素耐药性无关。其他三种氨基酸变异(HtrA中的T278I,Upps中的K101E和FmtC中的Q692E)存在于大多数(87.5%–93.8%)的hVISA和VISA分离物中,但仅少数(22.9%–25.7%)分离的VSSA,表明它们与万古霉素耐药性有关。

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