Regulation of the Edwardsiella tarda hemolysin gene and luxS by EthR.
Edwardsiella tarda is a pathogen with a broad host range that includes human and animals. The E. tarda hemolysin (Eth) system, which comprises EthA and EthB, is a noted virulence element that is widely distributed in pathogenic isolates of E. tarda. Previous study has shown that the expression of ethB is regulated by iron, which suggests the possibility that the ferric uptake regulator (Fur) is involved in the regulation of ethB. The work presented in this report supports the previous findings and demonstrates that ethB expression was decreased under conditions when the E. tarda Fur (Fur(Et)) was overproduced, and enhanced when FurEt was inactivated. We also identified a second ethB regulator, EthR, which is a transcription regulator of the GntR family. EthR represses ethB expression by direct interaction with the ethB promoter region. In addition to ethB, EthR also modulates, but positively, luxS expression and AI-2 production by binding to the luxS promoter region. The expression of ethR itself is subject to negative autoregulation; interference with this regulation by overexpressing ethR during the process of infection caused (i) drastic changes in ethB and luxS expressions, (ii) vitiation in the tissue dissemination and survival ability of the bacterium, and (iii) significant attenuation of the overall bacterial virulence. These results not only provide new insights into the regulation mechanisms of the Eth hemolysin and LuxS/AI-2 quorum sensing systems but also highlight the importance of these systems in bacterial virulence.
Wang
Fang
F
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China.
Zhang
Min
M
Hu
Yong-hua
YH
Zhang
Wei-wei
WW
Sun
Li
L
D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013437:Carbon-Sulfur Lyases / Q000096:biosynthesis* / Q000235:genetics; D020609:Edwardsiella tarda / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000382:microbiology*; D005432:Flounder; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria