CRISPR-Cas Adaptation in Pathogenic Mycobacteria: Implications for Virulence and Immune Evasion

Abstract

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their respective (Cas) proteins are part of the adaptive immune system that helps to identify and suppress invading genetic components in bacteria. The CRISPR-Cas system has recently become one of the possible determinants of virulence and immune evasion in pathogenic Mycobacterium species, especially Mycobacterium tuberculosis and Mycobacterium abscessus. This paper examines the structure of CRISPR-Cas loci, their acquisition patterns and functional dynamics of CRISPR-Cas loci in clinically relevant mycobacterial strains. Comparative genomic studies indicate the specific distribution of the cas genes in the lineages, which indicates the selection pressure associated with the host adaptation and environmental survival. Spacer profiling reveals that there is common acquisition of sequences based on bacteriophages and plasmids, which indicates the role of the system in ensuring the retention of genomic integrity during immune pressure. Transcriptomic evidence also indicates a difference in Cas gene expression in the context of macrophage infection with the implication of a regulatory cross-talk between CRISPR elements and host-responsive responses. According to functional studies, CRISPR-mediated control might tune the expression of genes that are linked to cell wall remodelling and antigen presentation, thus enabling escape of the host immune system. Taken together, these results suggest that the CRISPR-Cas system of pathogenic mycobacteria goes beyond antiviral protection to control virulence, stress resistance, and immune regulation. These adaptive mechanisms have been shown to understand mycobacterial pathogenesis and create new opportunities to develop CRISPR-based diagnostic or therapeutic treatments of latent and drug-resistant infections.