Antimicrobial resistance patterns and genetic elements associated with the antibiotic resistance of Helicobacter pylori strains from Shanghai

Abstract

Background Shanghai, in east China, has one of the world’s highest burdens of Helicobacter pylori infection. While multidrug regimens can effectively eradicate H. pylori, the increasing prevalence of antibiotic resistance (AR) in H. pylori has been recognized by the WHO as ‘high priority’ for urgent need of new therapies. Moreover, the genetic characteristics of H. pylori AR in Shanghai is under-reported. The purpose of this study was to determine the resistance prevalence, re-substantiate resistance-conferring mutations, and investigate novel genetic elements associated with H. pylori AR. Results We performed whole genome sequencing and antimicrobial susceptibility testing of 112 H. pylori strains isolated from gastric biopsy specimens from Shanghai patients with different gastric diseases. No strains were resistant to amoxicillin. Levofloxacin, metronidazole and clarithromycin resistance was observed in 39 (34.8%), 73 (65.2%) and 18 (16.1%) strains, respectively. There was no association between gastroscopy diagnosis and resistance phenotypes. We reported the presence or absence of several subsystem protein coding genes including hopE, hofF, spaB, cagY and pflA, and a combination of CRISPRs, which were potentially correlated with resistance phenotypes. The H. pylori strains were also annotated for 80 genome-wide AR genes (ARGs). A genome-wide ARG analysis was performed for the three antibiotics by correlating the phenotypes with the genetic variants, which identified the well-known intrinsic mutations conferring resistance to levofloxacin (N87T/I and/or D91G/Y mutations in gyrA), metronidazole (I38V mutation in fdxB), and clarithromycin (A2143G and/or A2142G mutations in 23S rRNA), and added 174 novel variations, including 23 non-synonymous SNPs and 48 frameshift Indels that were significantly enriched in either the antibiotic-resistant or antibiotic-susceptible bacterial populations. The variant-level linkage disequilibrium analysis highlighted variations in a protease Lon with strong co-occurring correlation with a series of resistance-associated variants. Conclusion Our study revealed multidrug antibiotic resistance in H. pylori strains from Shanghai, which was characterized by high metronidazole and moderate levofloxacin resistance, and identified specific genomic characteristics in relation to H. pylori AR. Continued surveillance of H. pylori AR in Shanghai is warranted in order to establish appropriate eradication treatment regimens for this population.

Evolutionary History and Strength of Selection Determine the Rate of Antibiotic Resistance Adaptation

“…Lon has been shown in vitro to modify drug-resistance levels when there is a loss of function ( Matange 2020 ; Zou et al 2021 ). Both proteins, ClpX and Lon, have been associated with increased resistance ( Bæk et al 2014 ; Liu et al 2022 ).…”

Revealing the novel effect of Jinghua Weikang capsule against the antibiotic resistance of Helicobacter pylori

“…Resistance of H. pylori to MTZ is more common than that of other antibiotics ( Gerrits et al, 2006 ; Ho et al, 2022 ). MTZ resistance rates range from 42 to 96% worldwide, with higher rates in developing countries ( Geng et al, 2022 ; Ho et al, 2022 ; Liu et al, 2022 ; Tian et al, 2022 ; Veenendaal et al, 2022 ). In triple, quadruple, and sequential therapies, including MTZ, eradication failure is often associated with MTZ resistance ( Fischbach and Evans, 2007 ; Gatta et al, 2009 ).…”

Physiologically‐based pharmacokinetic modelling to predict intragastric rifabutin concentrations in the treatment of Helicobacter pylori infection

“…H. pylori infection is a leading cause of peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa‐associated lymphoid tissue (MALT) lymphoma; successful eradication is associated with the reduced risk of these outcomes 1 . However, eradication of H. pylori has become increasingly difficult due to alarming contemporary antibiotic resistance rates, the reasons for which are multifactorial 2 . Since H. pylori is predominantly located in the gastric lumen and luminal crypts, relatively high doses of orally administered antibiotics are necessary for effective treatment 3 …”