Polymorphism of virulence genes and biofilm associated with in vitro induced resistance to clarithromycin in Helicobacter pylori

Gut Pathogens

Research

Mun Fai Loke¹  Naim Asyraf Rosli²  Anis Rageh Al-Maleki³  Mohammed Abdelfatah Alhoot⁴  Jamuna Vadivelu⁵  Eng Guan Chua⁶ 

[1] Camtech Biomedical Pte Ltd, Singapore, Singapore;Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia;Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia;Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen;Faculty of Pharmacy, Airlangga University, 60155, Surabaya, Indonesia;School of Graduate Studies, Management & Science University, Shah Alam, Selangor, Malaysia;Medical Education Research and Development Unit, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia;School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Perth, WA, Australia;

关键词: Helicobacter pylori;    Whole genome sequencing;    Virulence;    Biofilm formation;    Antibiotic resistance;    Clarithromycin;   

DOI  :  10.1186/s13099-023-00579-4

 received in 2023-08-02, accepted in 2023-10-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundClarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed.ResultsThe S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production.ConclusionsTherefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.

【 授权许可】

CC BY   
© The Author(s) 2023

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