Antimicrobial Resistance and Genetic Characteristics that Might be Related to Antibiotic Resistance of 112 Helicobacter Pylori Shanghai Isolates

Abstract Background Shanghai, east China has one of the world’s highest burdens of Helicobacter pylori infection. While multidrug regimens can effectively eradicate H. pylori , antibiotic-resistant (AR) 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 might be related to H. pylori AR. Results We performed a whole-genomic and phenotypic analysis of 112 H. pylori isolated from gastric biopsy specimens from a population with different gastric diseases and residing in Shanghai. No strains were resistant to amoxicillin. Levofloxacin, metronidazole and clarithromycin resistance was observed in 39, 73 and 18 isolates, respectively. There was no association between gastroscopy diagnosis and resistance phenotypes. We reported the presence or absence of several subsystem proteins including hopE , hofF , spaB , cagY and pflA , and a combination of CRISPRs, which were potentially correlated with resistance phenotypes. The H. pylori isolates were also annotated for AR genes to define a resistome containing 80 genes. A resistome-wide association study (RWAS) was performed for the three antibiotics by correlating the phenotypes with the variation data. The RWAS correctly identified the well-known intrinsic resistance associated mutations for 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, with 23 nsSNPs and 48 fsIndels significantly enriched in resistant or susceptible populations. The variant-level linkage disequilibrium analysis demonstrated a series of variations with strong co-occurring correlation with known mutations, and highlighted the underlying role of a protease Lon. Conclusion Our study indicated H. pylori isolates from Shanghai exhibit multidrug antibiotic resistance, and identified specific genomic characteristics in relation to H. pylori AR in Shanghai. Continued surveillance of H. pylori AR in Shanghai is warranted in order to establish appropriate eradication treatment regimens for this population.