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Kooshapour, H.

Publications and source records attributed to Kooshapour, H..

2 recordsLinked to original sources
bioRxiv2025

3'UTR-derived small RNA couples acid resistance to metabolic reprogramming of Salmonella within macrophages

Acid resistance is crucial for enterobacteria to withstand host acidic environments during infection, including the gastrointestinal tract and macrophage phagosomes. A key acid resistance mechanism of the facultative intracellular pathogen Salmonella is expression of the arginine decarboxylase AdiA. While AdiA confers acid resistance via an H+-consuming reaction, we discover that the 3'-untranslated region (UTR) of adiA mRNA is processed by RNase E into a regulatory small RNA, AdiZ. Through RNA-RNA interactome profiling and transcriptomic analysis, followed by in vitro structural probing and in vivo validations, we demonstrate that AdiZ directly base-pairs with and negatively regulates ptsG, pykF, and dmsA mRNAs involved in glucose uptake, glycolysis, and anaerobic respiration, respectively. Intriguingly, AdiZ is induced and facilitates Salmonella survival within macrophages, where acidic and hypoxic stresses prevail. Thus, simultaneous expression of AdiA and AdiZ from a single mRNA ties arginine-dependent acid resistance to metabolic reprogramming of Salmonella in the host intracellular niches. HIGHLIGHTSO_LISalmonella adiA transcript expresses both acid resistance enzyme and sRNA AdiZ C_LIO_LIAdiZ derived from the adiA 3'UTR is induced under an acidic and anaerobic condition C_LIO_LIAdiZ base-pairs with mRNAs to modulate glucose metabolism and anaerobic respiration C_LIO_LIAdiZ promotes Salmonella survival in acidic and hypoxic macrophage vacuoles C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/658255v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10aec22org.highwire.dtl.DTLVardef@14b5f2org.highwire.dtl.DTLVardef@1b53c8dorg.highwire.dtl.DTLVardef@19a8540_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗
bioRxiv2025

Intramacrophage RIL-seq uncovers an RNA antagonist of the Salmonella virulence-associated small RNA PinT

Salmonella virulence chiefly relies upon two major pathogenicity islands, SPI-1 and SPI-2, which enable host cell invasion and intracellular survival, respectively. There has been increasing evidence for post-transcriptional control of SPI gene expression by Hfq-dependent small RNAs (sRNAs) such as PinT. This 80-nucleotide sRNA is highly expressed after Salmonella enters host cells and modulates the transition from the SPI-1 to SPI-2 program by targeting different virulence factor mRNAs. It has been elusive, however, how PinT activity could be counteracted when virulence gene suppression were to be relieved. To identify putative inhibitors of PinT, we have mapped the RNA interactome of Salmonella recovered from infected macrophages, using an optimized version of the RIL-seq method. Next to offering an unprecedented view of Hfq-mediated RNA interactions during Salmonellas intracellular infection stage, RIL-seq uncovered the 3 end-derived sRNA InvS as a direct negative regulator of PinT. Biochemical and genetic experiments suggest a decoy mechanism whereby InvS lifts the PinT-mediated repression of virulence factors. Additionally, InvS acts as an mRNA repressor of the host cell adhesion protein, MipA, and PinT interaction with InvS relieves mipA repression. Together, our work identifies a unique pair of antagonistic sRNAs in a growing post-transcriptional network of virulence gene regulation.

microbiology↗