Proteomic analysis of the pathogen surface in cholera identifies host proteins involved in defense and microbiota recognition

Abdelrahim Zoued
Brigham and Women’s Hospital, Harvard Medical School, Cambridge, USA

Proteomic analysis of the pathogen surface in cholera identifies host proteins involved in defense and microbiota recognition

Many of the key interactions between pathogen and host during infection take place on the pathogen cell surface. Although these interactions are often important determinants of the outcome of infection, interrogating this critical host-pathogen interface in the setting of infection has been extremely challenging. Cell surface proteomics enabled a high-resolution definition of this interaction surface in an infant rabbit model of cholera. We designed and optimized a means to purify, identify, and quantitatively compare Vibrio cholerae cell surface proteins present in culture and during infection. This approach also identified the rabbit proteins bound to the pathogen in vivo, yielding an unprecedented perspective on the host response to infection. One of the host proteins bound to the pathogen surface in vivo was SP-D, a C-type lectin that has been linked to innate defense of the lung. Using SP-D knockout mice we found that SP-D also acts as an intestinal defense factor. Other V. cholerae-bound host proteins also bound distinct taxa of the murine intestinal microbiota. Proteomic investigation of the microbial surface-host interface should be a valuable tool for probing microbe-host interactions and their influence on homeostasis and infection.

Selected references

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