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

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Gastroenterology Report 2019年第1期7卷 42-49,I0002页

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 The Marshall Centre for Infectious Diseases Research and Training University of Western AustraliaPerthWestern AustraliaAustralia School of Biomedical Sciences Faculty of Health and Medical SciencesUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Medical Microbiology University of MalayaKuala LumpurWilayah PersekutuanMalaysia Shenzhen Dapeng New District Kuichong People Hospital ShenzhenGuangdongChina UM Marshall Centre University of MalayaKuala LumpurWilayah PersekutuanMalaysia School of Computer Science and Software Engineering University of Western AustraliaPerthWestern AustraliaAustralia

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.

关键词： Helicobacter pylori metronidazole antibiotic resistance whole-genome sequencing core protein clusters sequence alignment

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