Mycobacterium tuberculosis Peptidyl Prolyl Isomerase A Interacts With Host Integrin Receptor to Exacerbate Disease Progression. (13th February 2021)

• Record Type: Journal Article
• Authors: Dubey, Neha; Khan, Mehak Zahoor; Kumar, Suresh; Sharma, Aditya; Das, Lahari; Bhaduri, Asani; Singh, Yogendra; Nandicoori, Vinay Kumar
• Is Part Of: Journal of infectious diseases. Volume 224:Number 8(2021)
• Page Start: 1383
• Page End: 1393
• Publication Date: 2021-02-13
• Subjects: tuberculosis -- virulence -- secretion -- PPiA -- chaperone -- integrin -- matrix metalloproteinases; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab081
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Attenuated intracellular survival of Mycobacterium tuberculosis ( Mtb ) secretory gene mutants exemplifies their role as virulence factors. Mtb peptidyl prolyl isomerase A (PPiA) assists in protein folding through cis/trans isomerization of prolyl bonds. Here, we show that PPiA abets Mtb survival and aids in disease progression by exploiting host-associated factors. While the deletion of PPiA has no discernable effect on bacillary survival in a murine infection model, it compromises the formation of granuloma-like lesions and promotes host cell death through ferroptosis. Overexpression of PPiA enhances the bacillary load and exacerbates pathology in mice lungs. Importantly, PPiA interacts with the integrin α5β1 receptor through a conserved surface-exposed RGD motif. The secretion of PPiA as well as interaction with integrin contributes to disease progression by upregulating multiple host matrix metalloproteinases. Collectively, we identified a novel nonchaperone role of PPiA that is critical in facilitating host–pathogen interaction and ensuing disease progression. Abstract : Mycobacterium tuberculosis encodes for a Peptidyl prolyl isomerase A (PPiA) that is secreted through its N-terminal secretion signal. Secreted PPiA interacts with host integrin via arginine-glycine-aspartic acid motif, resulting in the upregulation of matrix metalloproteinases facilitating intracellular bacillary survival.