The RNA chaperone Hfq is essential for the virulence of <i>Salmonella typhimurium</i>

TLDR

Hfq is a bacterial RNA chaperone originally known for phage replication, now recognized as a central regulator of virulence gene expression in Salmonella through a network of small non‑coding RNAs. This study aimed to determine whether Hfq controls the expression and secretion of virulence factors in *Salmonella typhimurium*. The authors generated an hfq deletion strain and examined its effects on invasion, intracellular growth, motility, outer membrane protein expression, and envelope stress response, linking these phenotypes to post‑transcriptional regulation by small RNAs. Loss of Hfq caused marked attenuation in mice, severe defects in epithelial cell invasion and growth in both epithelial cells and macrophages, independent of RpoS, and induced a chronic RpoE‑mediated envelope stress response, underscoring Hfq’s role in multiple virulence traits.

Abstract

Summary The RNA chaperone, Hfq, plays a diverse role in bacterial physiology beyond its original role as a host factor required for replication of Q β RNA bacteriophage. In this study, we show that Hfq is involved in the expression and secretion of virulence factors in the facultative intracellular pathogen, Salmonella typhimurium . A Salmonella hfq deletion strain is highly attenuated in mice after both oral and intraperitoneal infection, and shows a severe defect in invasion of epithelial cells and a growth defect in both epithelial cells and macrophages in vitro . Surprisingly, we find that these phenotypes are largely independent of the previously reported requirement of Hfq for expression of the stationary phase sigma factor, RpoS. Our results implicate Hfq as a key regulator of multiple aspects of virulence including regulation of motility and outer membrane protein (OmpD) expression in addition to invasion and intracellular growth. These pleiotropic effects are suggested to involve a network of regulatory small non‐coding RNAs, placing Hfq at the centre of post‐transcriptional regulation of virulence gene expression in Salmonella . In addition, the hfq mutation appears to cause a chronic activation of the RpoE‐mediated envelope stress response which is likely due to a misregulation of membrane protein expression.