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Abstract：
We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the \'Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)\', while ARG-ACC-the ARG in the accessory genome-are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.
摘要：
我们进行了一项全球规模的研究，以鉴定幽门螺杆菌抗微生物耐药基因（ARG），解决他们的全球分布，了解其对临床分离菌耐药性(AMR)表型的影响。我们使用几种众所周知的工具针对广泛的细菌ARG数据库鉴定了ARG，然后分析了他们与来自不同国家的几十名患者的临床抗菌谱数据的相关性。这表明，结合多种工具和数据库，然后从注释结果中手动选择ARG，产生比单独使用单一工具或数据库更有决定性的结果。策展后，结果显示,幽门螺杆菌对11种不同的抗生素有42种ARG(16种与单一抗生素类耐药相关的基因和26种与多药耐药相关的基因).进一步的分析显示，幽门螺杆菌在核心基因组中天然含有ARG，称为“幽门螺杆菌核心基因组中常见的ARG集（ARG-CORE）”，而ARG-ACC-辅助基因组中的ARG-是特定菌株独有的。此外,我们检测到29个潜在外排泵相关AMR基因,这些基因主要被归类为ARG-CORE.从地理或幽门螺杆菌种群的角度来看，ARG分布似乎几乎相似；然而，一些ARG具有独特的分布，因为它们往往仅在特定地区或人群中发现。最后,我们证明,ARG的存在可能与临床患者分离株的敏感/耐药表型无直接相关,但可能影响最小抑制浓度表型.
