The role of Mce proteins in Mycobacterium avium paratuberculosis infection

• Published in: Scientific reports Vol. 14; no. 1; pp. 14964 - 15
• Main Authors: Blake, Rosemary, Jensen, Kirsty, Mabbott, Neil, Hope, Jayne, Stevens, Joanne
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-06-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/337; Animals; Bacterial Adhesion; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cattle; Cell Line; Chronic infection; E coli; Effector cells; Enteritis; Enteroids; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Escherichia coli; Escherichia coli - metabolism; Humanities and Social Sciences; Humans; Mammalian cell entry gene; Microbial-cell interaction; Monocytes; multidisciplinary; Mycobacteria; Mycobacterium avium paratuberculosis; Mycobacterium avium ssp paratuberculosis; Mycobacterium avium subsp. paratuberculosis - metabolism; Paratuberculosis; Paratuberculosis - microbiology; Proteins; Science; Science (multidisciplinary); Small intestine; THP-1 Cells; ssp; Mammalian cell entry gene; Enteroids; Microbial-cell interaction; MAP; Mycobacteria; Mycobacterium avium ssp paratuberculosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65592-2

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 bacterium to adhere to, and be internalised by, cells of the intestinal tract. The effector molecules expressed by MAP for this purpose remain to be fully identified and understood. Mammalian cell entry (mce) proteins have been shown to enable other Mycobacterial species to attach to and invade host epithelial cells. Here, we have expressed Mce1A, Mce1D, Mce3C and Mce4A proteins derived from MAP on the surface of a non-invasive
Escherichia coli
to characterise their role in the initial interaction between MAP and the host. To this end, expression of
mce1A
was found to significantly increase the ability of the
E. coli
to attach and survive intracellularly in human monocyte-like THP-1 cells, whereas expression of
mce1D
was found to significantly increase attachment and invasion of
E. coli
to bovine epithelial cell-like MDBK cells, implying cell-type specificity. Furthermore, expression of Mce1A and Mce1D on the surface of a previously non-invasive
E. coli
enhanced the ability of the bacterium to infect 3D bovine basal-out enteroids. Together, our data contributes to our understanding of the effector molecules utilised by MAP in the initial interaction with the host, and may provide potential targets for therapeutic intervention.