Role of Mce proteins inMycobacterium avium paratuberculosisinfection

Abstract

AbstractMycobacterium aviumsubspeciesparatuberculosis(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-invasiveE. colihost to characterise their role in the initial interaction between MAP and the host. To this end,mce1Awas found to significantly increase the ability of theE. colito attach and survive intracellularly in THP-1 cells, andmce1Dwas found to significantly increase attachment and invasion of MDBK cells. Both genes were implicated in the increased ability ofE. colito infect 3D bovine basal-out enteroids. Together, these results have identified two effector molecules used by MAP with a degree of cell-type specificity.