Exploring the antibiofilm efficacy of pyrimidines against Vibrio parahaemolyticus, mechanisms and their potential food processing applications

Vibrio parahaemolyticus is a significant seafood-borne enteropathogen with a global concern. Its propensity for biofilm formation has increased capacity for seafood contamination and risk of infection, thus requiring new control strategies. This study determined the potentials of pyrimidines to control V. parahaemolyticus biofilms, virulence and defining their mechanisms and applications. Among the 37 pyrimidines evaluated, 2,4-dichloro-5-fluoropyrimidine, 5-bromo-2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine and 2,4-dichloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine showed significant antibiofilm effects, with minimum inhibitory concentrations at 40, 50 and 50 μg/mL respectively. The hits showed significant bactericidal effects, eradicated preformed biofilms, and impaired key pathogenic attributes, including adhesion factors. They were bactericidal to other Vibrios and demonstrated the capacity to protect food and contact materials against Vibrio biofilm. Further studies revealed the synergistic potentials, safety and cell membrane as well as transcriptional regulator as assailable antimicrobial targets of the pyrimidines. Thus, our findings unveiled pyrimidine analogs as potent antimicrobial agents to control V. parahaemolyticus challenges in food or related industries. •Antibiofilm and antibacterial activities of pyrimidines against V. parahaemolyticus.•Pyrimidines attenuated virulence factors including hemolysin and siderophore production.•Pyrimidines induced ROS-mediated cell death, repressed gene expression and targeted protein in-silico.•Pyrimidines demonstrated synergism with antibiotics, food additive and evaded resistance evolution.•Pyrimidines showed potential to protect seafood and contact materials against biofilms.