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Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force
INTRODUCTION: Antimicrobial resistance, especially the development of multidrug-resistant strains, is an urgent public health threat. Antibiotic adjuvants have been shown to improve the treatment of resistant bacterial infections. METHODS: We verified that exogenous L-arginine promoted the killing e...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546041/ https://www.ncbi.nlm.nih.gov/pubmed/37795291 http://dx.doi.org/10.3389/fmicb.2023.1237825 |
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author | Zhu, Chunyang Zhou, Yanhong Kang, Jian Yang, Heng Lin, Jinglin Fang, Binghu |
author_facet | Zhu, Chunyang Zhou, Yanhong Kang, Jian Yang, Heng Lin, Jinglin Fang, Binghu |
author_sort | Zhu, Chunyang |
collection | PubMed |
description | INTRODUCTION: Antimicrobial resistance, especially the development of multidrug-resistant strains, is an urgent public health threat. Antibiotic adjuvants have been shown to improve the treatment of resistant bacterial infections. METHODS: We verified that exogenous L-arginine promoted the killing effect of gentamicin against Salmonella in vitro and in vivo, and measured intracellular ATP, NADH, and PMF of bacteria. Gene expression was determined using real-time quantitative PCR. RESULTS: This study found that alkaline arginine significantly increased gentamicin, tobramycin, kanamycin, and apramycin-mediated killing of drug-resistant Salmonella, including multidrug-resistant strains. Mechanistic studies showed that exogenous arginine was shown to increase the proton motive force, increasing the uptake of gentamicin and ultimately inducing bacterial cell death. Furthermore, in mouse infection model, arginine effectively improved gentamicin activity against Salmonella typhimurium. DISCUSSION: These findings confirm that arginine is a highly effective and harmless aminoglycoside adjuvant and provide important evidence for its use in combination with antimicrobial agents to treat drug-resistant bacterial infections. |
format | Online Article Text |
id | pubmed-10546041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105460412023-10-04 Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force Zhu, Chunyang Zhou, Yanhong Kang, Jian Yang, Heng Lin, Jinglin Fang, Binghu Front Microbiol Microbiology INTRODUCTION: Antimicrobial resistance, especially the development of multidrug-resistant strains, is an urgent public health threat. Antibiotic adjuvants have been shown to improve the treatment of resistant bacterial infections. METHODS: We verified that exogenous L-arginine promoted the killing effect of gentamicin against Salmonella in vitro and in vivo, and measured intracellular ATP, NADH, and PMF of bacteria. Gene expression was determined using real-time quantitative PCR. RESULTS: This study found that alkaline arginine significantly increased gentamicin, tobramycin, kanamycin, and apramycin-mediated killing of drug-resistant Salmonella, including multidrug-resistant strains. Mechanistic studies showed that exogenous arginine was shown to increase the proton motive force, increasing the uptake of gentamicin and ultimately inducing bacterial cell death. Furthermore, in mouse infection model, arginine effectively improved gentamicin activity against Salmonella typhimurium. DISCUSSION: These findings confirm that arginine is a highly effective and harmless aminoglycoside adjuvant and provide important evidence for its use in combination with antimicrobial agents to treat drug-resistant bacterial infections. Frontiers Media S.A. 2023-09-19 /pmc/articles/PMC10546041/ /pubmed/37795291 http://dx.doi.org/10.3389/fmicb.2023.1237825 Text en Copyright © 2023 Zhu, Zhou, Kang, Yang, Lin and Fang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Zhu, Chunyang Zhou, Yanhong Kang, Jian Yang, Heng Lin, Jinglin Fang, Binghu Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force |
title | Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force |
title_full | Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force |
title_fullStr | Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force |
title_full_unstemmed | Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force |
title_short | Alkaline arginine promotes the gentamicin-mediated killing of drug-resistant Salmonella by increasing NADH concentration and proton motive force |
title_sort | alkaline arginine promotes the gentamicin-mediated killing of drug-resistant salmonella by increasing nadh concentration and proton motive force |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546041/ https://www.ncbi.nlm.nih.gov/pubmed/37795291 http://dx.doi.org/10.3389/fmicb.2023.1237825 |
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