Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics

IntroductionVibrio parahaemolyticus is a foodborne pathogen commonly found in seafood, and drug resistance poses significant challenges to its control. This study aimed to identify novel drug targets for antibacterial drug discovery.MethodsTo identify drug targets, we performed a pan-genome analysis...

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Main Authors: Wenbin Liu, Peiyu Ou, Fangyuan Tian, Jingyang Liao, Yan Ma, Jie Wang, Xiaobao Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1218176/full
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author Wenbin Liu
Wenbin Liu
Peiyu Ou
Peiyu Ou
Fangyuan Tian
Fangyuan Tian
Jingyang Liao
Jingyang Liao
Yan Ma
Yan Ma
Jie Wang
Jie Wang
Xiaobao Jin
Xiaobao Jin
author_facet Wenbin Liu
Wenbin Liu
Peiyu Ou
Peiyu Ou
Fangyuan Tian
Fangyuan Tian
Jingyang Liao
Jingyang Liao
Yan Ma
Yan Ma
Jie Wang
Jie Wang
Xiaobao Jin
Xiaobao Jin
author_sort Wenbin Liu
collection DOAJ
description IntroductionVibrio parahaemolyticus is a foodborne pathogen commonly found in seafood, and drug resistance poses significant challenges to its control. This study aimed to identify novel drug targets for antibacterial drug discovery.MethodsTo identify drug targets, we performed a pan-genome analysis on 58 strains of V. parahaemolyticus genomes to obtain core genes. Subsequently, subtractive proteomics and physiochemical checks were conducted on the core proteins to identify potential therapeutic targets. Molecular docking was then employed to screen for anti-V. parahaemolyticus compounds using a in-house compound library of Streptomyces parvus, chosen based on binding energy. The anti-V. parahaemolyticus efficacy of the identified compounds was further validated through a series of experimental tests.Results and DiscussionPangenome analysis of 58 V. parahaemolyticus genomes revealed that there were 1,392 core genes. After Subtractive proteomics and physiochemical checks, Flagellar motor switch protein FliN was selected as a therapeutic target against V. parahaemolyticus. FliN was modeled and docked with Streptomyces parvus source compounds, and Actinomycin D was identified as a potential anti-V. parahaemolyticus agent with a strong binding energy. Experimental verification confirmed its effectiveness in killing V. parahaemolyticus and significantly inhibiting biofilm formation and motility. This study is the first to use pan-genome and subtractive proteomics to identify new antimicrobial targets for V. parahaemolyticus and to identify the anti-V. parahaemolyticus effect of Actinomycin D. These findings suggest potential avenues for the development of new antibacterial drugs to control V. parahaemolyticus infections.
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spelling doaj.art-957e865400b84d11b63c630cf9541cc52023-07-06T14:52:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-07-011410.3389/fmicb.2023.12181761218176Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomicsWenbin Liu0Wenbin Liu1Peiyu Ou2Peiyu Ou3Fangyuan Tian4Fangyuan Tian5Jingyang Liao6Jingyang Liao7Yan Ma8Yan Ma9Jie Wang10Jie Wang11Xiaobao Jin12Xiaobao Jin13School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, ChinaIntroductionVibrio parahaemolyticus is a foodborne pathogen commonly found in seafood, and drug resistance poses significant challenges to its control. This study aimed to identify novel drug targets for antibacterial drug discovery.MethodsTo identify drug targets, we performed a pan-genome analysis on 58 strains of V. parahaemolyticus genomes to obtain core genes. Subsequently, subtractive proteomics and physiochemical checks were conducted on the core proteins to identify potential therapeutic targets. Molecular docking was then employed to screen for anti-V. parahaemolyticus compounds using a in-house compound library of Streptomyces parvus, chosen based on binding energy. The anti-V. parahaemolyticus efficacy of the identified compounds was further validated through a series of experimental tests.Results and DiscussionPangenome analysis of 58 V. parahaemolyticus genomes revealed that there were 1,392 core genes. After Subtractive proteomics and physiochemical checks, Flagellar motor switch protein FliN was selected as a therapeutic target against V. parahaemolyticus. FliN was modeled and docked with Streptomyces parvus source compounds, and Actinomycin D was identified as a potential anti-V. parahaemolyticus agent with a strong binding energy. Experimental verification confirmed its effectiveness in killing V. parahaemolyticus and significantly inhibiting biofilm formation and motility. This study is the first to use pan-genome and subtractive proteomics to identify new antimicrobial targets for V. parahaemolyticus and to identify the anti-V. parahaemolyticus effect of Actinomycin D. These findings suggest potential avenues for the development of new antibacterial drugs to control V. parahaemolyticus infections.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1218176/fullpan-genomeVibrio parahaemolyticussubtractive proteomicsStreptomyces parvusbioflim
spellingShingle Wenbin Liu
Wenbin Liu
Peiyu Ou
Peiyu Ou
Fangyuan Tian
Fangyuan Tian
Jingyang Liao
Jingyang Liao
Yan Ma
Yan Ma
Jie Wang
Jie Wang
Xiaobao Jin
Xiaobao Jin
Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
Frontiers in Microbiology
pan-genome
Vibrio parahaemolyticus
subtractive proteomics
Streptomyces parvus
bioflim
title Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
title_full Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
title_fullStr Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
title_full_unstemmed Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
title_short Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
title_sort anti vibrio parahaemolyticus compounds from streptomyces parvus based on pan genome and subtractive proteomics
topic pan-genome
Vibrio parahaemolyticus
subtractive proteomics
Streptomyces parvus
bioflim
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1218176/full
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