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

Autor: Sharma N; Department of Biological Sciences, Birla Institute of Technology & Science, Pilani, Rajasthan, 333031, India., Das A; Department of Biological Sciences, Birla Institute of Technology & Science, Pilani, Rajasthan, 333031, India., Nair AV; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India., Sethi P; Department of Biological Sciences, Birla Institute of Technology & Science, Pilani, Rajasthan, 333031, India., Negi VD; Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Punjab, 140306, India., Chakravortty D; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, 560012, India., Marathe SA; Department of Biological Sciences, Birla Institute of Technology & Science, Pilani, Rajasthan, 333031, India. sandhya.marathe@pilani.bits-pilani.ac.in.
Jazyk: angličtina
Zdroj: Gut pathogens [Gut Pathog] 2024 Oct 26; Vol. 16 (1), pp. 63. Date of Electronic Publication: 2024 Oct 26.
DOI: 10.1186/s13099-024-00653-5
Abstrakt: 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 phox-/- macrophages, suggesting the system's role in the pathogens' antioxidant defense. We deduced that the CRISPR-Cas system positively regulates H 2 O 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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