LTB4virulence24-03-29submit.xlsx

The relationship between antibiotic resistance and bacterial virulence is not fully explored. In this study, we perform proteomic analysis of oxytetracycline-resistant Edwardsiella tarda (LTB4-ROTC). Compared to oxytetracycline-sensitive E. tarda (LTB4-S), LTB4-ROTC has 234 differentially expressed proteins, which are enriched to the pathways of Type III secretion system, Type VI secretion system and flagellum. The abundance of the proteins of these pathways are all down-regulated in LTB4-ROTC. Further functional analysis of the virulent phenotypes, including auto-aggregation, biofilm formation, hemolysis, swimming and swarming, are impaired in LTB4-ROTC, validating the reduced pathways. Furthermore, the in vivo bacterial challenge in both of tilapia and zebrafish infection models suggest that the virulence of LTB4-ROTC is attenuated. In addition, analysis of the immune gene expression show that LTB4-ROTC induces stronger immune response in spleen but weaker response in head kidney than those induced by LTB4-S. Then, zebrafish and tilapia are challenged with sub-lethal dose of LTB4-ROTC as live vaccine followed by LTB4-S challenge. The relative percentage of survival of zebrafish is 60% and of tilapia is 75% after vaccination. Thus, our study suggest that bacteria acquiring antibiotic resistance may attenuate virulence, which can be explored as potential live vaccine.