Abstract：
The relationship between antibiotic resistance and bacterial virulence has not yet been fully explored. Here, we use Edwardsiella tarda as the research model to investigate the proteomic change upon oxytetracycline resistance (LTB4-ROTC). Compared to oxytetracycline-sensitive E. tarda (LTB4-S), LTB4-ROTC has 234 differentially expressed proteins, of which the abundance of 84 proteins is downregulated and 15 proteins are enriched to the Type III secretion system, Type VI secretion system, and flagellum pathways. Functional analysis confirms virulent phenotypes, including autoaggregation, biofilm formation, hemolysis, swimming, and swarming, are impaired in LTB4-ROTC. Furthermore, the in vivo bacterial challenge in both tilapia and zebrafish infection models suggests that the virulence of LTB4-ROTC is attenuated. Analysis of immune gene expression shows that LTB4-ROTC induces a stronger immune response in the spleen but a weaker response in the head kidney than that induced by LTB4-S, suggesting it\'s a potential vaccine candidate. Zebrafish and tilapia were challenged with a sublethal dose of LTB4-ROTC as a live vaccine followed by LTB4-S challenge. The relative percentage of survival of zebrafish is 60% and that of tilapia is 75% after vaccination. Thus, our study suggests that bacteria that acquire antibiotic resistance may attenuate virulence, which can be explored as a potential live vaccine to tackle bacterial infection in aquaculture.
摘要：
抗生素耐药性与细菌毒力之间的关系尚未得到充分探讨。这里,我们以塔达爱德华氏菌为研究模型，研究土霉素耐药性（LTB4-ROTC）的蛋白质组学变化。与土霉素敏感E.tarda（LTB4-S）相比，LTB4-ROTC有234个差异表达蛋白,其中84种蛋白质的丰度被下调，15种蛋白质被富集到III型分泌系统中，VI型分泌系统,和鞭毛途径。功能分析证实了毒力表型，包括自动聚合，生物膜的形成，溶血,游泳,蜂拥而至，在LTB4-ROTC中受损。此外，罗非鱼和斑马鱼感染模型中的体内细菌攻击表明LTB4-ROTC的毒力减弱。免疫基因表达分析表明，LTB4-ROTC在脾脏中诱导的免疫反应更强，而在头肾中的免疫反应比LTB4-S诱导的弱。这表明它是一个潜在的候选疫苗。用亚致死剂量的LTB4-ROTC作为活疫苗攻击斑马鱼和罗非鱼，然后进行LTB4-S攻击。接种后，斑马鱼的相对存活率为60％，罗非鱼的相对存活率为75％。因此，我们的研究表明，获得抗生素耐药性的细菌可能会减弱毒力，它可以作为一种潜在的活疫苗来解决水产养殖中的细菌感染。
