title: Use of next generation sequence to investigate potential novel macrolide resistance mechanisms in a population of Moraxella catarrhalis isolates.
abstract: 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.
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Ya-Li
authors: YL
authors: Liu
authors: Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.|Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
authors: Dong-Fang
authors: DF
authors: Li
authors: Department of Clinical Laboratory, the First Affiliated Hospital of Xiamen University, Xiamen, China.
authors: He-Ping
authors: HP
authors: Xu
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Meng
authors: M
authors: Xiao
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Jing-Wei
authors: JW
authors: Cheng
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Zhi-Peng
authors: ZP
authors: Xu
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Xin-Xin
authors: XX
authors: Chen
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Ge
authors: G
authors: Zhang
authors: Charles Sturt University, Leeds Parade, Orange, New South Wales 2687, Australia.|Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales 2145, Australia.
authors: Timothy
authors: T
authors: Kudinha
authors: Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales 2145, Australia.
authors: Fanrong
authors: F
authors: Kong
authors: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.|Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
authors: Yan-Ping
authors: YP
authors: Gong
authors: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.|Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
authors: Xin-Ying
authors: XY
authors: Wang
authors: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.|Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
authors: Yin-Xin
authors: YX
authors: Zhang
authors: Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.|Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
authors: Hong-Long
authors: HL
authors: Wu
authors: Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China.
authors: Ying-Chun
authors: YC
authors: Xu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000235:genetics*; D058885:Multilocus Sequence Typing / Q000379:methods; D009154:Mutation / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D018942:Macrolides; D012338:RNA, Ribosomal, 23S