Where are the receptors?

Contributed by Poyin Chen

The first step in bacterial interaction with host cells is host recognition, followed by host adhesion. All of these initial interactions take place at the host cell surface; however, we have only scratched the surface of what is known about bacterial-host membrane interactions. This host recognition is usually initiated by a bacterial protein transiently binding to a transmembrane host protein. The association begins with receptors on the host cell binding ligands on the microbial cell to form a partnership that initiates responses in both cells. Methods to determine the specific cognate partnerships are lacking. The transient nature of this initial interaction is a main contributor to our lack of understanding in the initial interactions between a pathogen and its host. One method to elucidate these interactions is by covalently linking the bacterial protein to the host protein during interaction so that we can purify these receptor-ligand complexes for further study without disrupting their interaction. This method was developed by the Weimer lab to discover cognate host-microbe receptor/ligand pairs using a covalent cross-linking strategy with whole cells. We have been successfully implemented this method to identify novel bacterial-host receptor/ligand partnerships, of which many partnerships have been validated by independent research groups. The identification of these protein pairings allows us to define biologically important events that are triggered during association of the microbiome. Furthermore, knowing what these pairings are is critical in defining the initiating signal from the host membrane that results in pathology or commensal association.

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