Abstract
BackgroundClarithromycin (CLR) resistance has become a predominant factor for treatment failure of Helicobacter pylori eradication. Although the molecular mechanism of CLR resistance has been clearly understood in H. pylori, it is lack of evidence of other genes involved in drug resistance. Furthermore, the molecular mechanism of phenotype susceptible to CLR while genotype of 23S rRNA is mutant with A2143G is unclear. Here, we characterized the mutations of CLR-resistant and -susceptible H. pylori strains to explore bacterial resistance.MethodsIn the present study, the whole genomes of twelve clinical isolated H. pylori strains were sequenced, including two CLR-susceptible strains with mutation of A2143G. Single nucleotide variants (SNVs) were extracted and analyzed from multidrug efflux transporter genes.ResultsWe did not find mutations associated with known CLR-resistant sites except for controversial T2182C outside of A2143G in the 23S rRNA gene. Although total SNVs of multidrug efflux transporter gene and the SNVs of HP0605 were significant differences (P ≤ 0.05) between phenotype resistant and susceptible strains. There is no significant difference in SNVs of RND or MFS (HP1181) family. However, the number of mutations in the RND family was significantly higher in the mutant strain (A2143G) than in the wild type. In addition, three special variations from two membrane proteins of mtrC and hefD were identified in both CLR-susceptible strains with A2143G.ConclusionsNext-generation sequencing is a practical strategy for analyzing genomic variation associated with antibiotic resistance in H. pylori. The variations of membrane proteins of the RND family may be able to participate in the regulation of clinical isolated H. pylori susceptibility profiles.
Highlights
Clarithromycin (CLR) resistance has become a predominant factor for treatment failure of Helicobacter pylori eradication
Hirata et al reported that the MIC of CLR-resistant strains was decreased by using efflux pump inhibitor (EPI), indicating that in addition to the point mutation of 23S ribosomal RNA (rRNA) gene, the efflux pump cluster is involved in the development of resistance to CLR [16]
Genotype of 23S rRNA and phenotype of H. pylori resistant to CLR For twelve clinical isolated strains, CLR susceptibility testing indicated that the six of strains were susceptible to CLR and six of strains were resistant to CLR
Summary
Clarithromycin (CLR) resistance has become a predominant factor for treatment failure of Helicobacter pylori eradication. The studies suggest that some other point mutations may be involved in CLR resistance at position 2115G, G2141A, T2117C, T2182C, T2717C [9,10,11]. Another mechanism of resistance to CLR has been reported that five conserved families of multidrug efflux pump transporter contribute to bacterial antibiotic resistance. Hirata et al reported that the MIC of CLR-resistant strains was decreased by using efflux pump inhibitor (EPI), indicating that in addition to the point mutation of 23S rRNA gene, the efflux pump cluster is involved in the development of resistance to CLR [16]
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