Syed Shams ul Hassan ^* Huizi Jin

• Shanghai Jiao Tong University, Shanghai, China

The rise of bacterial infections and increasing antibiotic resistance underscores an urgent need for new, effective antimicrobial agents with marine bacteria offering a unique and promising source for novel antibiotic compounds to combat persistent and emerging pathogens. In this research, five compounds were achieved from marine Streptomyces sp, C2-13 and their yield was enhanced by the addition of zinc sulphate 0.5mM. All compounds have been evaluated for its antibacterial activity against multiple pathogens among which good activity was achieved against S.aureus, while potent activity was achieved against Riemerella anatipestifer with its IC50 value on 200 µm and bactericidal effect on 300 µm. Among all compounds, 4 was more active against both pathogens. Transcriptome analysis of active compound 4 showed its antibacterial effect on R. anatipestifer by inhibiting 30 and 50S ribosomal subunits, resistance mechanisms and gliding motility proteins IX secretion system (T9SS), interfering with protein translations process, secretion system, defense and resistance mechanisms, ultimately resulting in effective inhibition of normal bacterial growth and its motility. To investigate the anti-bacterial mechanism, all compounds were docked with two enzymes, and TLR-4 protein for predicting vaccine construct, and the best docking score was achieved against RMFP with the highest score of -12.9 for compound 4. In-silico cloning was carried out to ensure the expression of proteins generated and were cloned using E.coli as a host. The simulation studies have shown that both compound 4-RMFP and TLR-4-RMFP complex are stable with the system. To best known to our knowledge this is the first study investigating marine bacterial metabolites against R. anatipestifer with their anti-bacterial mechanism and enhancing its yield through addition of zinc sulphate ions.