Fig. 6

Deletion of the CRISPR-Cas system attenuates Salmonella pathogenicity. Proposed mechanisms of the type I-E CRISPR-Cas system in regulating Salmonella pathogenesis via modulation of SPI-1 and SPI-2 genes. We propose that the CRISPR-Cas system positively regulates hilA (direct regulation via complementary base-pairing between crRNA and gene) whereby it upregulates the expression of SPI-1 apparatus and effector proteins (direct regulation of sipA) involved in the invasion of enterocytes by Salmonella. The intestinal epithelial cells reinforce the intestinal barrier function by releasing antimicrobial peptides. The CRISPR-Cas system appears to indirectly regulate (red dotted lines) pmr genes to provide resistance against antimicrobial peptides (AMPs). Within the Salmonella containing vacuole (SCV) of macrophages, the bacteria shut down its SPI-1 system and activates the SPI-2-encoded SsrAB system in response to the acidic milieu. The SsrAB system further activates the SPI-2 encoded genes. The CRISPR-Cas may be positively regulating SsrB (direct regulation) to trigger activation of SPI-2 encoded structural genes and effector proteins (direct regulation of pipB2) to aid intracellular proliferation and survival of Salmonella. In addition, the CRISRP-Cas system negatively regulates OmpW (direct regulation) during oxidative stress, thereby aiding in Salmonella’s survival. Taken together, the CRISPR-Cas system positively regulates Salmonella pathogenesis. The figure was created using Biorender