Exploring the Molecular Mechanisms of Macrolide Resistance in Laboratory Mutant <i>Helicobacter pylori</i>

• Main Authors: Meltem Ayaş (Author), Sinem Oktem-Okullu (Author), Orhan Özcan (Author), Tanıl Kocagöz (Author), Yeşim Gürol (Author)
• Format: Book
• Published: MDPI AG, 2024-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of <i>Helicobacter pylori</i> infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in <i>H. pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i> genome for the first time, emphasizing their potential as targets for advanced studies.

Item Description

10.3390/antibiotics13050396
2079-6382