Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny
Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny
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DOI：
10.1111/hel.12782
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发表时间：
2021-01-25
期刊：
影响因子：
4.4
通讯作者：
Moran-Gilad, Jacob
中科院分区：
文献类型：
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作者：
Domanovich-Asor, Tal;Craddock, Hillary A.;Moran-Gilad, Jacob
背景幽门螺杆菌耐药性（AMR）在全球范围内不断增加，可导致治疗失败和抗生素使用不当。本研究利用全基因组测序技术对H. pylori耐药基因组和幽门螺杆菌基因组。pylori分离株序列。通过内部生物信息学管道对AMR相关基因（pbp 1A、23 S rRNA、gyrA、rdxA、frxA和rpoB）的点突变进行分析，并使用核心基因组多位点序列分型（cgMLST）进行PCR基因组分析。pylori基因组，但在个别分支上的分离株之间观察到超过1000个基因座的大距离。耐药基因组分析揭示了以前发现的与表型抗生素耐药性相关的常见突变的流行;每个基因最常见的点突变是S589 G（pbp 1A，48.8%的完美比对序列），A2143 G（23 S rRNA，27.4%的完全比对序列），N87 K\I\Y（gyrA，14.7%的完全比对序列），R131 K（rdxA，65.7%的完全比对序列）和C193 S（frxA，62.6%的序列完全对齐）。结论这是迄今为止最大规模的研究，其特征在于H. pylori与H.幽门螺杆菌耐药基因组基于>1000基因组。结合联合收割机WGS和表型方法的进一步分析将提供对突变和抗性之间关联的进一步理解。
Background Antimicrobial resistance (AMR) in Helicobacter pylori is increasing globally and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to conduct an analysis of the H. pylori resistome and phylogeny.Materials/methods A total of 1040 H. pylori isolate sequences were retrieved. Analysis was conducted via an in-house bioinformatics pipeline targeting point mutations in selected genes frequently associated with AMR (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) and phylogenomic analyses using core genome multilocus sequence typing (cgMLST).Results Phylogenomic analysis revealed a notable geographical clustering of H. pylori genomes across world regions, but large distances of more than 1000 loci between isolates on individual branches were observed. Resistome analysis revealed the prevalence of common mutations which have previously been found to correlate with phenotypic antibiotic resistance; the most common point mutations for each gene were S589G (pbp1A, 48.8% of perfect aligned sequences), A2143G (23S rRNA, 27.4% of perfectly aligned sequences), N87 K\I\Y (gyrA, 14.7% of perfectly aligned sequences), R131K (rdxA, 65.7% of perfectly aligned sequences), and C193S (frxA, 62.6% of perfectly aligned sequences).Conclusions This is the largest study to date featuring the global phylogeny of H. pylori in conjunction with a global snapshot of the H. pylori resistome based on >1000 genomes. Further analyses that combine WGS and phenotypic methods will provide further understanding of the association between the mutations and resistance.