Liu Ya-Li, Li Dong-Fang, Xu He-Ping, Xiao Meng, Cheng Jing-Wei, Zhang Li, Xu Zhi-Peng, Chen Xin-Xin, Zhang Ge, Kudinha Timothy, Kong Fanrong, Gong Yan-Ping, Wang Xin-Ying, Zhang Yin-Xin, Wu Hong-Long, Xu Ying-Chun
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
Sci Rep. 2016 Oct 24;6:35711. doi: 10.1038/srep35711.
Although previous studies have confirmed that 23S rRNA gene mutation could be responsible for most of macrolide resistance in M. catarrhalis, a recent study suggested otherwise. Next generation sequence based comparative genomics has revolutionized the mining of potential novel drug resistant mechanisms. In this study, two pairs of resistant and susceptible M. catarrhalis isolates with different multilocus sequence types, were investigated for potential differential genes or informative single nucleotide polymorphisms (SNPs). The identified genes and SNPs were evaluated in 188 clinical isolates. From initially 12 selected differential genes and 12 informative SNPs, 10 differential genes (mboIA, mcbC, mcbI, mboIB, MCR_1794, MCR_1795, lgt2B/C, dpnI, mcbB, and mcbA) and 6 SNPs (C619T of rumA, T140C of rplF, G643A of MCR_0020, T270G of MCR_1465, C1348A of copB, and G238A of rrmA) were identified as possibly linked to macrolide resistance in M. catarrhalis. Most of the identified differential genes and SNPs are related to methylation of ribosomal RNA (rRNA) or DNA, especially MCR_0020 and rrmA. Further studies are needed to determine the function and/or evolution process, of the identified genes or SNPs, to establish whether some novel or combined mechanisms are truly involved in M. catarrhalis macrolide resistance mechanism.
尽管先前的研究已经证实23S rRNA基因突变可能是卡他莫拉菌对大环内酯类耐药的主要原因，但最近的一项研究却提出了不同的观点。基于新一代测序的比较基因组学彻底改变了潜在新型耐药机制的挖掘方式。在本研究中，对两对具有不同多位点序列类型的卡他莫拉菌耐药和敏感分离株进行了研究，以寻找潜在的差异基因或信息性单核苷酸多态性（SNP）。在188株临床分离株中对鉴定出的基因和SNP进行了评估。从最初选定的12个差异基因和12个信息性SNP中，鉴定出10个差异基因（mboIA、mcbC、mcbI、mboIB、MCR_1794、MCR_1795、lgt2B/C、dpnI、mcbB和mcbA）和6个SNP（rumA的C619T、rplF的T140C、MCR_0020的G643A、MCR_1465的T270G、copB的C1348A和rrmA的G238A）可能与卡他莫拉菌对大环内酯类的耐药性有关。大多数鉴定出的差异基因和SNP与核糖体RNA（rRNA）或DNA的甲基化有关，尤其是MCR_0020和rrmA。需要进一步研究来确定所鉴定基因或SNP的功能和/或进化过程，以确定是否有一些新的或联合的机制真正参与了卡他莫拉菌的大环内酯类耐药机制。
