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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Frontiers Media S.A.
2023-07-01
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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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publishDate | 2023-07-01 |
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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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