Exploring the Molecular Mechanisms of Macrolide Resistance in Laboratory Mutant Helicobacter pylori

• Published in: Antibiotics (Basel) Vol. 13; no. 5; p. 396
• Main Authors: Ayaş, Meltem, Oktem-Okullu, Sinem, Özcan, Orhan, Kocagöz, Tanıl, Gürol, Yeşim
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26-04-2024
• Subjects: Antibiotic resistance; Antibiotics; Bacteria; Cancer therapies; Clarithromycin; Cross-resistance; Developing countries; Dilution; Drug resistance; Gastric cancer; Gene sequencing; Genes; Genomes; Gram-negative bacteria; H. pylori; Helicobacter pylori; Infections; Laboratories; LDCs; macrolide resistance; Molecular modelling; Mutants; Mutation; Next-generation sequencing; Protein synthesis; Proteins; rRNA; rRNA 23S; Sulfite; Whole genome sequencing; Turkey; H. pylori; clarithromycin; next-generation sequencing; macrolide resistance
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics13050396

Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of
infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in
are associated with point mutations in 23S ribosomal RNA (rRNA), the relationships of other mutations with resistance remain unclear. We examined possible new macrolide resistance mechanisms in resistant strains using next-generation sequencing. Two resistant strains were obtained from clarithromycin-susceptible
following exposure to low clarithromycin concentrations using the agar dilution method. Sanger sequencing and whole-genome sequencing were performed to detect resistance-related mutations. Both strains carried the A2142G mutation in 23S rRNA. Candidate mutations (T1495A, T1494A, T1490A, T1476A, and G1472T) for clarithromycin resistance were detected in the Mutant-1 strain. Furthermore, a novel mutation in the gene encoding for the sulfite exporter TauE/SafE family protein was considered to be linked to clarithromycin resistance or cross-resistance, being identified as a target for further investigations. In the Mutant-2 strain, a novel mutation in the gene that encodes DUF874 family protein that can be considered as relevant with antibiotic resistance was detected. These mutations were revealed in the
genome for the first time, emphasizing their potential as targets for advanced studies.