The small RNA pint contributes to phop-mediated regulation of the salmonella pathogenicity island 1 type III secretion system in salmonella enterica serovar typhimurium

Salmonella enterica serovar Typhimurium induces inflammatory diarrhea and bacterial uptake into intestinal epithelial cells using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). HilA activates transcription of the SPI1 structural components and effector proteins. Expression of hilA is activated by HilD, HilC, and RtsA, which act in a complex feed-forward regulatory loop. Many environmental signals and other regulators are integrated into this regulatory loop, primarily via HilD. After the invasion of Salmonella into host intestinal epithelial cells or during systemic replication in macrophages, the SPI T3SS is no longer required or expressed. We have shown that the two-component regulatory system PhoPQ, required for intracellular survival, represses the SPI1 T3SS mostly by controlling the transcription of hilA and hilD. Here we show that PinT, one of the PhoPQ-regulated small RNAs (sRNAs), contributes to this regulation by repressing hilA and rtsA translation. PinT base pairs with both the hilA and rtsA mRNAs, resulting in translational inhibition of hilA, but also induces degradation of the rts transcript. PinT also indirectly represses expression of FliZ, a posttranslational regulator of HilD, and directly represses translation of ssrB, encoding the primary regulator of the SPI2 T3SS. Our in vivo mouse competition assays support the concept that PinT controls a series of virulence genes at the posttranscriptional level in order to adapt Salmonella from the invasion stage to intracellular survival.