Lin Lee-Chung, Chang Shih-Cheng, Ge Mao-Cheng, Liu Tsui-Ping, Lu Jang-Jih
Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Infect Drug Resist. 2018 Jan 18;11:113-123. doi: 10.2147/IDR.S148335. eCollection 2018.
Prolonged vancomycin usage may cause methicillin-resistant to become vancomycin-intermediate (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 (VSSA), 41 hVISA and 16 VISA isolates revealed 29 single-nucleotide variations in 12 genes (, , , , , , , , , , and ) 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.
长期使用万古霉素可能导致耐甲氧西林金黄色葡萄球菌变为万古霉素中介金黄色葡萄球菌（VISA）和异质性万古霉素中介金黄色葡萄球菌（hVISA）。VISA和hVISA对万古霉素耐药的机制仍不清楚。在本研究中，对30株万古霉素敏感金黄色葡萄球菌（VSSA）、41株hVISA和16株VISA分离株的核苷酸序列变异分析显示，12个与细胞壁合成或双组分系统相关的基因（ 、 、 、 、 、 、 、 、 、 、 和 ）中有29个单核苷酸变异。这29个单核苷酸变异中有6个是新发现的，导致了以下氨基酸变化：FmtC中的Q692E；HtrA中的T278I、P306L和I311T；Upps中的I63V和K101E。由于HtrA中的P306L和I311T以及Upps中的I63V存在于大多数（76.7%-86.7%）的VSSA分离株中，这三个氨基酸变异可能与万古霉素耐药性无关。其他三个氨基酸变异（HtrA中的T278I、Upps中的K101E和FmtC中的Q69L）存在于大多数（87.5%-93.8%）的hVISA和VISA分离株中，但仅存在于少数（22.9%-25.7%）的VSSA分离株中，这表明它们与万古霉素耐药性有关。
