Bai Bing, Lin Zhiwei, Pu Zhangya, Xu Guangjian, Zhang Fan, Chen Zhong, Sun Xiang, Zheng Jinxin, Li Peiyu, Deng Qiwen, Yu Zhijian
Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infections, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
Quality Control Center of Hospital Infection Management of Shenzhen, Shenzhen Nanshan People's Hospital, Guangdong Medical University, Shenzhen, China.
Front Microbiol. 2019 Nov 8;10:2546. doi: 10.3389/fmicb.2019.02546. eCollection 2019.
Omadacycline (Omad), a new tetracycline (Tet)-class broad-spectrum aminomethylcycline, has been reported to exhibit excellent potency against Gram-positive bacteria, including and Enterococci. The aim of this study was to evaluate the activity and heteroresistance characteristics of Omad in clinical isolates from China and investigate Omad resistance mechanisms. A sample of 263 non-duplicate clinical isolates [127 methicillin-resistant (MRSA) and 136 methicillin-sensitive (MSSA)] were collected retrospectively. Our data indicated that Omad exhibited excellent activity against both MRSA and MSSA. Omad heteroresistance frequencies were 3.17% (4/126) in MRSA and 12.78% (17/133) in MSSA. No mutations in Tet target sites, (five 16SrRNA copies and 30S ribosomal protein S10) were present in heteroresistance-derived clones, whereas Tet target site mutations contribute to induced Omad resistance in . RNA sequencing (RNA-Seq) revealed that overexpression of branched-chain amino acid transport system II carrier protein and Na/Pi cotransporter family protein contributes to Omad heteroresistance emergence. Whole-genome sequencing demonstrated that the genetic mutation of fibronectin-binding protein (FnBP) could increase the Omad MIC. In conclusion, Omad heteroresistance risk should be considered in clinical isolates with MICs ≥ 0.5 mg/L and Omad susceptibility in may be affected by efflux pump proteins (i.e., a branched-chain amino acid transport system II carrier protein and an Na/Pi cotransporter family protein), and FnBP.
奥马环素（Omad）是一种新型四环素类广谱氨基甲基环素，据报道，它对革兰氏阳性菌，包括[具体细菌名称未给出]和肠球菌，具有优异的抗菌活性。本研究旨在评估奥马环素在中国临床分离株中的抗菌活性和异质性耐药特征，并探究奥马环素的耐药机制。回顾性收集了263株非重复临床分离株样本[127株耐甲氧西林金黄色葡萄球菌（MRSA）和136株甲氧西林敏感金黄色葡萄球菌（MSSA）]。我们的数据表明，奥马环素对MRSA和MSSA均表现出优异的抗菌活性。奥马环素在MRSA中的异质性耐药频率为3.17%（4/126），在MSSA中为12.78%（17/133）。在异质性耐药衍生克隆中，四环素靶点位点（五个16SrRNA拷贝和30S核糖体蛋白S10）未出现突变，而四环素靶点位点突变会导致[具体细菌名称未给出]对奥马环素产生诱导性耐药。RNA测序（RNA-Seq）显示，支链氨基酸转运系统II载体蛋白和钠/磷酸盐共转运蛋白家族蛋白的过表达促成了奥马环素异质性耐药的出现。全基因组测序表明，纤连蛋白结合蛋白（FnBP）的基因突变可增加奥马环素的最低抑菌浓度（MIC）。总之，对于MIC≥0.5mg/L的临床分离株，应考虑奥马环素异质性耐药风险，[具体细菌名称未给出]对奥马环素的敏感性可能受外排泵蛋白（即支链氨基酸转运系统II载体蛋白和钠/磷酸盐共转运蛋白家族蛋白）以及FnBP的影响。
