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

Abstract

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.

Antibacterial Ingredients and Modes of the Methanol-Phase Extract from the Fruit of Amomum villosum Lour.

“…The Gram-negative bacterium V. parahemolyticus is a leading sea-food-borne pathogen worldwide, and common clinical symptoms include headache, nausea, vomiting, and diarrhea. Severe infections caused by V. parahemolyticus can develop into sepsis or even death [ 17 ].…”

Detection of multidrug resistant Vibrio parahaemolyticus and anti-Vibrio Streptomyces sp. MUM 178J

“…is a group of filamentous Gram-positive mycelial Actinobacteria that are well-established candidates with antimicrobial, antioxidant, anticancer and immunosuppressant effects [157][158][159][160][161][162][163][164] . Their ability to produce a myriad of compounds piques the interest of researchers to identify valuable compounds that could hinder the growth of Vibrios [143,[165][166][167] . In the cross-streak assay, Streptomyces MUM 178J demonstrated antagonistic effects against MDR V. parahaemolyticus, RP0132.…”

“…An anti-V. parahaemolyticus compound, Actinomycin D was discovered in Streptomyces parvus during molecular docking studies done by Liu et al [165] . Actinomycin D was proposed to bind strongly to the flagellar motor switch protein FliN of V. parahaemolyticus, thereby impairing its motility and preventing biofilm formation [165] . You et al [166] isolated several Streptomyces sp.…”