Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori

作     者：Eng-Guan Chua Aleksandra W.Debowski KMary Webberley Fanny Peters Binit Lamichhane Mun-Fai Loke Jamuna Vadivelu Chin-Yen Tay Barry J.Marshall Michael J.Wise 

作者机构：The Marshall Centre for Infectious Diseases Research and TrainingUniversity of Western AustraliaPerthWestern AustraliaAustralia School of Biomedical SciencesFaculty of Health and Medical SciencesUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Medical MicrobiologyUniversity of MalayaKuala LumpurWilayah PersekutuanMalaysia Shenzhen Dapeng New District Kuichong People HospitalShenzhenGuangdongChina UM Marshall CentreUniversity of MalayaKuala LumpurWilayah PersekutuanMalaysia School of Computer Science and Software EngineeringUniversity of Western AustraliaPerthWestern AustraliaAustralia 

出 版 物：《Gastroenterology Report》 (胃肠病学报道（英文）)

年 卷 期：2019年第7卷第1期

页      面：42-49,I0002页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：This project was supported by ShenZhen’s Sanming Project(Grant No:SZSM201510050) University of Malaya-Ministry of Education(UM-MoE)High Impact Research(HIR)grant(reference UM.C/625/1/HIR/MoE/CHAN13/3,Account No.H-50001-A000030) a National Health and Medical Research Council(NHMRC)Sir McFarlane Burnett Fellowship grant(572723)to B.J.M.,the Vice Chancellor of the University of Western Australia,and the Western Australian Department of Commerce and Department of Health.A.W.D.was supported by an Early Career Research Fellowship from the NHMRC(APP1073250) 

主　　题：Helicobacter pylori metronidazole antibiotic resistance whole-genome sequencing core protein clusters sequence alignment 

摘      要：Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori ***,the global emergence of metronidazole resistance in Hp poses a major challenge to health *** of RdxA is known to be a major mechanism of conferring metronidazole resistance in ***,metronidazole resistance can also arise in *** strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this ***:We performed whole-genome sequencing on 121 *** clinical strains,among which 73 were ***-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was *** sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in ***:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant *** of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole *** sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in *** that merit further investigation.