Proteomic Insights Into Moxifloxacin Efficacy and Resistance in Vibrio parahaemolyticus

The emergence of multidrug-resistant Vibrio parahaemolyticus poses major public health challenges, necessitating new treatment strategies. This research uses quantitative proteomics to explore the underlying antibiotic stress response mechanisms of moxifloxacin (Mox), a broad-spectrum fluoroquinolone, which effectively targets clinically resistant strains. After exposing bacteria to 1/2 MIC of Mox (2.5 ng/ml), proteomic analysis revealed significant changes in differentially expressed proteins (DEPs). These DEPs were enriched in several gene ontology (GO) and KEGG pathways, including SOS responses, cellular response to external stimuli, DNA helicase complexes, and transmembrane transport. KEGG analysis also indicated involvement in alanine, aspartate, and glutamate metabolism. PPI analysis revealed that many DEPs participated in quorum sensing (VP0047, VP0048, VP2088, VP0050, VP0049, and VP2091 downregulated), amino acid metabolism (VP1772, VP0483, VP0481, VP0826, ArgH, VP0484 downregulated, while CarA and CarB were upregulated), and kinase activity (VP0364, VP0365, VP0366, VP1190 downregulated; VP0370, VP1688, VPA0094, VPA0095, MltD, and Flg2 upregulated). Under Mox treatment, V. parahaemolyticus increased production of fluoroquinolone resistance proteins (VP1315 and VPA0095) and multidrug efflux components (VPA1190 and VPA1191), shifting from efflux-based resistance toward DNA repair mechanisms that maintain genome stability under fluoroquinolone stress. These proteomic findings confirm the primary bactericidal effect of Mox and reveal stress responses that could precede stress response. Overall, this profiling offers insights for optimizing fluoroquinolone therapy and developing additional treatments to combat resistance in V. parahaemolyticus infections.