Volatile Organic Compounds (VOCs) Protect from Fish Pathogen Sp.: A Combined In Vitro, In Vivo, and In Silico Approach

Antibiotic resistance is an alarming threat all over the world, and the biofilm formation efficacy of bacteria is making the situation worse. The antagonistic efficacy of against one of the known fish pathogens, sp., is examined in this study. Moreover, sp.'s biofilm formation ability and in vivo pathogenicity on are also justified here. Firstly, six selected bacterial strains were used to obtain antimicrobial compounds against this pathogenic strain. Among those, , another pathogenic bacterium, surprisingly demonstrated remarkable antagonistic activity against sp. in both in vitro and in vivo assays. The biofilm distrusting potentiality of 's cell-free supernatants (CFSs) was likewise found to be around 56%. Furthermore, the volatile compounds of were identified by GC-MS in order to explore compounds with antibacterial efficacy against sp. through an in silico study, where 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) (PDB: 5B7P) was chosen as a target protein for its unique characteristics and pathogenicity. Several volatile compounds, such as oxime- methoxy-phenyl-, fluoren-9-ol, 3,6-dimethoxy-9-(2-phenylethynyl)-, and 2H-indol-2-one, 1,3-dihydro- showed a strong binding affinity, with free energy of -6.7, -7.1, and -6.4 Kcal/mol, respectively, in complexes with the protein MTAN. Moreover, the root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, and its potential compounds can be employed as an alternative to antibiotics for aquaculture, demonstrating their effectiveness in suppressing sp.