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CRISPR-Cas system positively regulates virulence of Salmonella enterica serovar Typhimurium

Authors :
Sharma, Nandita
Das, Ankita
Nair, Abhilash Vijay
Sethi, Palash
Negi, Vidya Devi
Chakravortty, Dipshikha
Marathe, Sandhya Amol
Source :
Gut Pathogens. October 26, 2024, Vol. 16 Issue 1
Publication Year :
2024

Abstract

Background Salmonella, a foodborne pathogen, possesses a type I-E clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated (Cas) system. We investigated the system's role in regulating Salmonella virulence by deleting the CRISPR arrays and Cas operon. Results Our study demonstrates invasion and proliferation defects of CRISPR-Cas knockout strains in intestinal epithelial cells and macrophages owing to the repression of invasion and virulence genes. However, proliferation defects were not observed in the Gp91.sup.phox-/- macrophages, suggesting the system's role in the pathogens' antioxidant defense. We deduced that the CRISPR-Cas system positively regulates H.sub.2O.sub.2 importer (OmpW), catalase (katG), peroxidase (ahpC), and superoxide dismutase (soda and sodCI), thereby protecting the cells from oxidative radicals. The knockout strains were attenuated in in-vivo infection models (Caenorhabditis elegans and BALB/c mice) due to hypersensitivity against antimicrobial peptides, complement proteins, and oxidative stress. The attenuation in virulence was attributed to the suppression of LPS modifying (pmr) genes, antioxidant genes, master regulators, and effectors of the SPI-1 (invasion) and SPI-2 (proliferation) islands in knockout strains. The regulation could be attributed to the partial complementarity of the CRISPR spacers with these genes. Conclusions Overall, our study extends our understanding of the role of the CRISPR-Cas system in Salmonella pathogenesis and its virulence determinants. Keywords: Salmonella, Type 1-E CRISPR-Cas system, Virulence, SPI-1-T3SS, SPI-2-T3SS, Anti-oxidant genes<br />Author(s): Nandita Sharma[sup.1], Ankita Das[sup.1], Abhilash Vijay Nair[sup.2], Palash Sethi[sup.1], Vidya Devi Negi[sup.3], Dipshikha Chakravortty[sup.2] and Sandhya Amol Marathe[sup.1] Introduction The bacterial adaptive immune system, Clustered Regularly Interspaced Short Palindromic [...]

Details

Language :
English
ISSN :
17574749
Volume :
16
Issue :
1
Database :
Gale General OneFile
Journal :
Gut Pathogens
Publication Type :
Academic Journal
Accession number :
edsgcl.813866026
Full Text :
https://doi.org/10.1186/s13099-024-00653-5