Trends in Helicobacter pylori resistance to clarithromycin: from phenotypic to genomic approaches

Autor: Filipa F. Vale, Andreia T. Marques, Andréa Cynthia Santos, Mónica Oleastro, Jorge M. B. Vítor
Přispěvatelé: Repositório da Universidade de Lisboa
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Microbial Genomics
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 2057-5858
Popis: For a long time Helicobacter pylori infections have been treated using the macrolide antibiotic, clarithromycin. Clarithromycin resistance is increasing worldwide and is the most common cause of H. pylori treatment failure. Here we review the mechanisms of antibiotic resistance to clarithromycin, detailing the individual and combinations of point mutations found in the 23S rRNA gene associated with resistance. Additionally, we consider the methods used to detect clarithromycin resistance, emphasizing the use of high-throughput next-generation sequencing methods, which were applied to 17 newly sequenced pairs of H. pylori strains isolated from the antrum and corpus of a recent colonized paediatric population. This set of isolates was composed of six pairs of resistant strains whose phenotype was associated with two point mutations found in the 23S rRNA gene: A2142C and A2143G. Other point mutations were found simultaneously in the same gene, but, according to our results, it is unlikely that they contribute to resistance. Further, among susceptible isolates, genomic variations compatible with mutations previously associated with clarithromycin resistance were detected. Exposure to clarithromycin may select low-frequency variants, resulting in a progressive increase in the resistance rate due to selection pressure.
F. F. V. is the recipient of a project grant (PTDC/BTM-SAL/28978/2017) from the Fundação para a Ciência e a Tecnologia (FCT), which supported this work. J. V.’s research group was financed by New England Biolabs, Inc. (USA).
Databáze: OpenAIRE