Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates

Antibiotic resistance (AMR) has always been a hot topic all over the world and its mechanisms are varied and complicated. Previous evidence revealed the metabolic slowdown in resistant bacteria, suggesting the important role of metabolism in antibiotic resistance. However, the molecular mechanism of...

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Autores principales:	Chunmei Shen, Ying Shen, Hui Zhang, Maosuo Xu, Leqi He, Jingbo Qie
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Klebsiella pneumoniae (K. pneumoniae) comparative proteomics bioinformatics metabolism antibiotic resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4c97951ee7664154a9659ea3ec7728fa
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spelling	oai:doaj.org-article:4c97951ee7664154a9659ea3ec7728fa2021-11-18T07:01:13ZComparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates1664-302X10.3389/fmicb.2021.773829https://doaj.org/article/4c97951ee7664154a9659ea3ec7728fa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.773829/fullhttps://doaj.org/toc/1664-302XAntibiotic resistance (AMR) has always been a hot topic all over the world and its mechanisms are varied and complicated. Previous evidence revealed the metabolic slowdown in resistant bacteria, suggesting the important role of metabolism in antibiotic resistance. However, the molecular mechanism of reduced metabolism remains poorly understood, which inspires us to explore the global proteome change during antibiotic resistance. Here, the sensitive, cotrimoxazole-resistant, amikacin-resistant, and amikacin/cotrimoxazole -both-resistant KPN clinical isolates were collected and subjected to proteome analysis through liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). A deep coverage of 2,266 proteins were successfully identified and quantified in total, representing the most comprehensive protein quantification data by now. Further bioinformatic analysis showed down-regulation of tricarboxylic acid cycle (TCA) pathway and up-regulation of alcohol metabolic or glutathione metabolism processes, which may contribute to ROS clearance and cell survival, in drug-resistant isolates. These results indicated that metabolic pathway alteration was directly correlated with antibiotic resistance, which could promote the development of antibacterial drugs from “target” to “network.” Moreover, combined with minimum inhibitory concentration (MIC) of cotrimoxazole and amikacin on different KPN isolates, we identified nine proteins, including garK, uxaC, exuT, hpaB, fhuA, KPN_01492, fumA, hisC, and aroE, which might contribute mostly to the survival of KPN under drug pressure. In sum, our findings provided novel, non-antibiotic-based therapeutics against resistant KPN.Chunmei ShenYing ShenHui ZhangMaosuo XuLeqi HeJingbo QieJingbo QieFrontiers Media S.A.articleKlebsiella pneumoniae (K. pneumoniae)comparative proteomicsbioinformaticsmetabolismantibiotic resistanceMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Klebsiella pneumoniae (K. pneumoniae) comparative proteomics bioinformatics metabolism antibiotic resistance Microbiology QR1-502
spellingShingle	Klebsiella pneumoniae (K. pneumoniae) comparative proteomics bioinformatics metabolism antibiotic resistance Microbiology QR1-502 Chunmei Shen Ying Shen Hui Zhang Maosuo Xu Leqi He Jingbo Qie Jingbo Qie Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
description	Antibiotic resistance (AMR) has always been a hot topic all over the world and its mechanisms are varied and complicated. Previous evidence revealed the metabolic slowdown in resistant bacteria, suggesting the important role of metabolism in antibiotic resistance. However, the molecular mechanism of reduced metabolism remains poorly understood, which inspires us to explore the global proteome change during antibiotic resistance. Here, the sensitive, cotrimoxazole-resistant, amikacin-resistant, and amikacin/cotrimoxazole -both-resistant KPN clinical isolates were collected and subjected to proteome analysis through liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). A deep coverage of 2,266 proteins were successfully identified and quantified in total, representing the most comprehensive protein quantification data by now. Further bioinformatic analysis showed down-regulation of tricarboxylic acid cycle (TCA) pathway and up-regulation of alcohol metabolic or glutathione metabolism processes, which may contribute to ROS clearance and cell survival, in drug-resistant isolates. These results indicated that metabolic pathway alteration was directly correlated with antibiotic resistance, which could promote the development of antibacterial drugs from “target” to “network.” Moreover, combined with minimum inhibitory concentration (MIC) of cotrimoxazole and amikacin on different KPN isolates, we identified nine proteins, including garK, uxaC, exuT, hpaB, fhuA, KPN_01492, fumA, hisC, and aroE, which might contribute mostly to the survival of KPN under drug pressure. In sum, our findings provided novel, non-antibiotic-based therapeutics against resistant KPN.
format	article
author	Chunmei Shen Ying Shen Hui Zhang Maosuo Xu Leqi He Jingbo Qie Jingbo Qie
author_facet	Chunmei Shen Ying Shen Hui Zhang Maosuo Xu Leqi He Jingbo Qie Jingbo Qie
author_sort	Chunmei Shen
title	Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
title_short	Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
title_full	Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
title_fullStr	Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
title_full_unstemmed	Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates
title_sort	comparative proteomics demonstrates altered metabolism pathways in cotrimoxazole- resistant and amikacin-resistant klebsiella pneumoniae isolates
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4c97951ee7664154a9659ea3ec7728fa
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Comparative Proteomics Demonstrates Altered Metabolism Pathways in Cotrimoxazole- Resistant and Amikacin-Resistant Klebsiella pneumoniae Isolates

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