The Serine Protease EspC from Enteropathogenic Escherichia coli Regulates Pore Formation and Cytotoxicity Mediated by the Type III Secretion System

Guignot, J., Segura, A. & Tran Van Nhieu, G. PLoS Pathogens 11, e1005013 (2015)

Speaker: Tsai-Yu, Wu (吳彩瑜)                                    Time: 14:00~15:00, Dec. 23, 2015

Commentator: Dr. I-Hsiu, Huang (黃一修老師)          Place: Room 601

Abstract

    Enteropahogenic Escherichia coli (EPEC) is an intestinal pathogen that causes diarrhea in infants with high morbidity rates in developing countries. Adherence of EPEC to mucosal intestinal epithelial cell and the formation of attaching and effacing (A/E) lesions result in destruction of the enterocyte microvilli¹. In addition, type III secretion system (T3SS) is a protein appendage and many Gram-negative bacteria employ T3SS to form the A/E lesions. T3SS is a hollow needle-like protein filament which is essential for the injection of bacterial virulence proteins into eukaryotic host cells². Furthermore, T3SS contains hydrophilic translocon proteins to connect to a hydrophobic component, allowing the insertion of T3SS into host cell membrane. The component of T3SS in EPEC consists of polymerized hydrophilic EspA, which connects the T3SS needle to hydrophobictranslocon proteins EspB and EspD. However, the regulatory mechanism of T3SS during EPEC infection is still unclear. EspC is one of T3SS components in EPEC and a serine protease autotransporter of Enterobacteriaceae (SPATE). The authors found that EspC preferentially targeted EspAassociated with EspD instead of EspA alone. Furthermore, EspC also controlled the amounts of EspA and EspD secretions in vitro or upon cell contact, but EspC did not influence EspA filament structures. Moreover, T3SS-mediated pore formation and cytotoxicity were also limited by EspC. Similarly, espC mutant showed that the levels of EspA and EspD and cytotoxicity were increased. In addition, the role of enterohaemorrhagic Escherichia coli (EHEC) EspP was similar to EspC. EspP can also target translocon proteins and cleave EspA and EspD, suggesting that EspP is also important to SPATEs. In conclusion, the authors reveal a T3SS-mediated regulatory mechanism of EPEC/EHEC.

References

1.         Cleary, J., et al. Enteropathogenic Escherichia coli (EPEC) adhesion to intestinal epithelial cells: role of bundle-forming pili (BFP), EspA filaments and intimin. Microbiology 150, 527-538 (2004).

2.         Loquet, A., et al. Atomic model of the type III secretion system needle. Nature 486, 276-279 (2012).