期刊
JOURNAL OF INFECTIOUS DISEASES
卷 224, 期 8, 页码 1383-1393出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab081
关键词
tuberculosis; virulence; secretion; PPiA; chaperone; integrin; matrix metalloproteinases
资金
- JC Bose fellowship [SB/S2/JCB-012/2015, JCB/2019/000015]
- Indian Council of Medical Research, Senior Research Fellowship
- D. S. Kothari postdoctoral fellowship
- Science and Engineering Research Board
- Tuberculosis Aerosol Challenge Facility at International Centre for Genetic Engineering and Biotechnology
PPiA not only assists in the survival of Mtb but also promotes disease progression by affecting host cell status through interaction with host-related factors.
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 alpha 5 beta 1 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.
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