title: An Edwardsiella tarda mutant lacking UDP-glucose dehydrogenase shows pleiotropic phenotypes, attenuated virulence, and potential as a vaccine candidate.
abstract: Edwarsiella tarda is highly resistant to the action of cationic antimicrobial peptides (CAMPs). However, the mechanism underlying CAMP resistance is not clear. The enzyme UDP-glucose dehydrogenase (Ugd) that converts UDP-glucose into UDP-glucuronic acid may be important for this resistance. In this study, a ugd gene was identified in E. tarda and its functional role was analyzed using an in-frame deletion mutant Δugd and the complemented strain ugd+. The lipopolysaccharide (LPS) produced by Δugd consisted of a truncated core oligosaccharide (OS) with no O-antigen attached. The ugd mutant was extremely sensitive to CAMPs, presumably because of alterations in LPS structure. The mutant also exhibited enhanced autoaggregation and biofilm formation and reduced hemolytic activity. Using different infection models we found that Δugd was impaired in survival within macrophages and displayed significantly attenuated virulence and an impaired ability to persist within the host. The expression of ugd was induced by polymyxin B and under the control of PhoP and RcsB, two response regulators of the bacterial two-component systems that we identified previously. Moreover, vaccination of turbot (Scophthalmus maximus) with Δugd by intraperitoneal injection elicited significant protection against the wild-type E. tarda strain, suggesting that Δugd may be promising as a potential vaccine candidate against edwardsiellosis.
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors: Yuanzhi
authors: Y
authors: Lv
authors: Junyuan
authors: J
authors: Zheng
authors: Minjun
authors: M
authors: Yang
authors: Qiyao
authors: Q
authors: Wang
authors: Yuanxing
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D020609:Edwardsiella tarda / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000517:prevention & control; D005393:Fish Diseases / Q000382:microbiology / Q000517:prevention & control; D005412:Flatfishes / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D042843:Glucose 1-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000235:genetics; D008264:Macrophages / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D019081:O Antigens / Q000737:chemistry; D010641:Phenotype; D011112:Polymyxin B / Q000494:pharmacology; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000235:genetics*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology / Q000592:standards; D014774:Virulence / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D019081:O Antigens; D014765:Viral Vaccines; D014533:Uridine Diphosphate Glucose Dehydrogenase; D042843:Glucose 1-Dehydrogenase; D011112:Polymyxin B