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Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance c...

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Autores principales: Fauzia, Kartika Afrida, Aftab, Hafeza, Tshibangu-Kabamba, Evariste, Alfaray, Ricky Indra, Saruuljavkhlan, Batsaikhan, Cimuanga-Mukanya, Alain, Matsumoto, Takashi, Subsomwong, Phawinee, Akada, Junko, Miftahussurur, Muhammad, Yamaoka, Yoshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952455/
https://www.ncbi.nlm.nih.gov/pubmed/36830189
http://dx.doi.org/10.3390/antibiotics12020279
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author Fauzia, Kartika Afrida
Aftab, Hafeza
Tshibangu-Kabamba, Evariste
Alfaray, Ricky Indra
Saruuljavkhlan, Batsaikhan
Cimuanga-Mukanya, Alain
Matsumoto, Takashi
Subsomwong, Phawinee
Akada, Junko
Miftahussurur, Muhammad
Yamaoka, Yoshio
author_facet Fauzia, Kartika Afrida
Aftab, Hafeza
Tshibangu-Kabamba, Evariste
Alfaray, Ricky Indra
Saruuljavkhlan, Batsaikhan
Cimuanga-Mukanya, Alain
Matsumoto, Takashi
Subsomwong, Phawinee
Akada, Junko
Miftahussurur, Muhammad
Yamaoka, Yoshio
author_sort Fauzia, Kartika Afrida
collection PubMed
description Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher’s exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori.
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spelling pubmed-99524552023-02-25 Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh Fauzia, Kartika Afrida Aftab, Hafeza Tshibangu-Kabamba, Evariste Alfaray, Ricky Indra Saruuljavkhlan, Batsaikhan Cimuanga-Mukanya, Alain Matsumoto, Takashi Subsomwong, Phawinee Akada, Junko Miftahussurur, Muhammad Yamaoka, Yoshio Antibiotics (Basel) Article Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher’s exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori. MDPI 2023-01-31 /pmc/articles/PMC9952455/ /pubmed/36830189 http://dx.doi.org/10.3390/antibiotics12020279 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fauzia, Kartika Afrida
Aftab, Hafeza
Tshibangu-Kabamba, Evariste
Alfaray, Ricky Indra
Saruuljavkhlan, Batsaikhan
Cimuanga-Mukanya, Alain
Matsumoto, Takashi
Subsomwong, Phawinee
Akada, Junko
Miftahussurur, Muhammad
Yamaoka, Yoshio
Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
title Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
title_full Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
title_fullStr Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
title_full_unstemmed Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
title_short Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
title_sort mutations related to antibiotics resistance in helicobacter pylori clinical isolates from bangladesh
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952455/
https://www.ncbi.nlm.nih.gov/pubmed/36830189
http://dx.doi.org/10.3390/antibiotics12020279
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