The WxxxE proteins in microbial pathogenesis

Abstract

Effector proteins secreted by pathogens modulate various host cellular processes and help in bacterial pathogenesis. Some of these proteins, injected by enteric pathogens via Type Three Secretion System (T3SS) were grouped together based on a conserved signature motif (WxxxE) present in them. The presence of WxxxE motif is not limited to effectors released by enteric pathogens or the T3SS but has been detected in non-enteric pathogens, plant pathogens and in association with Type II and Type IV secretion systems. WxxxE effectors are involved in actin organization, inflammation regulation, vacuole or tubule formation, endolysosomal signalling regulation, tight junction disruption, and apoptosis. The WxxxE sequence has also been identified in TIR [Toll/interleukin-1 (IL-1) receptor] domains of bacteria and host. In the present review, we have focussed on the established and predicted functions of WxxxE effectors secreted by several pathogens, including enteric, non-enteric, and plant pathogens.

Keywords:

• WxxxE motif
• effectors
• pathogens
• function
• TIR domains

Acknowledgments

The figure present in the manuscript is designed using www.biorender.com. We are grateful to Dr. Stella-Rita Ibeawuchi, Ms. Mahitha Shree Anandachar, and Dr. Stefania Tocci for providing suggestions during the preparation of the manuscript.

Author contributions

SA, SK, DL, and IMS have contributed to literature search, data collection and writing the manuscript. SA and DL have designed the figure. SA, IMS, and SD have revised the manuscript. SD supervised the study.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the National Institutes of Health (NIH) grants DK107585 and AG069689 (to SD). SD was supported by NIH/National Centre for Advancing Translational Sciences (NCATS) awards UG3TR002968, UG3TR003355, and R01-AI155696 and the Leona M. and Harry B. Helmsley Charitable Trust.