Role of Mce proteins in Mycobacterium avium paratuberculosis infection

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s Disease, a chronic granulomatous enteritis of ruminants. MAP establishes an infection in the host via the small intestine. This requires the bacteria to adhere to and be internalised by cells of the intestinal tract. The effector molecules expressed by MAP for this remain to be fully identified and understood. The mammalian cell entry (Mce) proteins play an essential role for other Mycobacterial species to facilitate the attachment and invasion of host epithelial cells. Here, we have expressed Mce1A, Mce1D, Mce3C and Mce4A proteins derived from MAP on the surface of a non-invasive E. coli host to characterise their role in the initial interaction between MAP and the host. To this end, mce1A was found to significantly increase the ability of the E. coli to attach and survive intracellularly in THP-1 cells, and mce1D was found to significantly increase attachment and invasion of MDBK cells. Both genes were implicated in the increased ability of E. coli to infect 3D bovine basal-out enteroids. Together, these results have identified two effector molecules used by MAP with a degree of cell-type specificity.

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