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

Autor: Nandita Sharma, Ankita Das, Abhilash Vijay Nair, Palash Sethi, Vidya Devi Negi, Dipshikha Chakravortty, Sandhya Amol Marathe
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Gut Pathogens, Vol 16, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 1757-4749
DOI: 10.1186/s13099-024-00653-5
Popis: 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 Gp91phox−/− macrophages, suggesting the system’s role in the pathogens’ antioxidant defense. We deduced that the CRISPR-Cas system positively regulates H2O2 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.
Databáze: Directory of Open Access Journals
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