Biology subjects

Altuvia, S.

Publications and source records attributed to Altuvia, S..

4 recordsLinked to original sources

bioRxiv2026

Functional decoding reveals a hidden regulatory layer of the Salmonella transcriptome during infection

Bacterial transcriptomes contain extensive, largely unexplored regulatory information beyond annotated genes, including small regulatory RNAs (sRNAs), yet distinguishing functionally active transcripts from the broader non-coding transcriptome remains a fundamental challenge, particularly in the context of host-pathogen interactions. Here, we develop an unbiased highthroughput functional screening strategy to decode the regulatory potential of the Salmonella enterica transcriptome during macrophage infection. A pooled expression library comprising 875 RNA fragments derived from infection-relevant conditions was screened for effects on bacterial invasion and intracellular survival, revealing distinct and stage-specific regulatory activities. Functional characterization uncovered non-canonical sRNAs originating from 5' untranslated regions that differentially modulate virulence-associated programs spanning the SPI-1, SPI-4 and SPI-2 pathogenicity islands. One attenuates the SPI-1 and SPI-4 secretion systems, limiting bacterial adhesion and invasion, whereas the other promotes invasion-associated programs while repressing pathways supporting intracellular survival. Rather than acting solely on individual virulence determinants, these regulatory activities reveal a broader layer of posttranscriptional control that coordinates bacterial adaptation across the dynamic host environment. Our study establishes a scalable strategy for extracting functional regulatory information from condition-specific bacterial transcriptomes and provides a framework for uncovering context-dependent RNA-mediated control of complex host-associated phenotypes.

microbiology↗

bioRxiv2024

Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition

SARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which extracellular NP on uninfected cells contributes to COVID-19 pathogenicity. We show that NP binds to cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of its RNA-binding sites facilitated by the flexible, positively charged, linker. Coating of uninfected lung-derived cells with purified NP attracted anti-NP-IgG from lung fluids and sera collected from COVID-19 patients. The magnitude of this immune recognition was significantly elevated in moderate compared to mild COVID-19 cases. Importantly, binding of anti-NP-IgG present in sera generated clusters that triggered C3b deposition by the classical complement pathway. Heparin analog enoxaparin outcompeted NP-binding, rescuing cells from anti-NP IgG-mediated complement deposition. Our findings unveil how extracellular NP may exacerbate COVID-19 tissue damage, and suggest leads for preventative therapy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/585388v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1084e20org.highwire.dtl.DTLVardef@4126caorg.highwire.dtl.DTLVardef@159c610org.highwire.dtl.DTLVardef@da7b7f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIIgG from patients sera target NP-bound cells resulting in complement activation C_LIO_LIThe flexible linker allows NP to both bind linear sulfated GAGs and wrap around RNA C_LIO_LIHeparin analogs prevent NP surface binding and alleviate complement activation C_LIO_LICell-ELISA anti-NP IgG levels differ between mild and moderate COVID-19 C_LI

immunology↗

bioRxiv2023

Balanced cell division is secured by two different regulatory sites in OxyS RNA

By interfering with cell division, the Escherichia coli oxidative stress-induced OxyS small RNA brings about cell cycle arrest thus allowing DNA damage repair. Cell division and cell elongation are opposing functions to the extent that inhibition of cell division requires a parallel inhibition of cell elongation for the cells to survive. In this study, we report that in addition to cell division OxyS inhibits mepS encoding an essential peptidoglycan endopeptidase responsible for cell elongation. Furthermore, a phylogenetic evolutionary target conservation analysis of OxyS homologs to identify OxyS most common function revealed that the majority of OxyS targets belong to the category of "cell cycle" followed by "peptidoglycan metabolism", especially cell elongation. mepS is the most frequent target of this category, predicted to be regulated by OxyS in 64 % of the 146 organisms studied. We suggest that cell cycle arrest and balancing between cell division and cell elongation are important and conserved functions of the oxidative stress induced sRNA OxyS.

microbiology↗

bioRxiv2020

RNA binding of Hfq monomers promotes RelA-mediated hexamerization in a limiting Hfq environment

The RNA chaperone Hfq acting as a hexamer, is a known mediator of post-transcriptional regulation expediting basepairing between small RNAs (sRNAs) and their target mRNAs. However, the intricate details associated with Hfq-RNA biogenesis are still unclear. Previously, we reported that the stringent response regulator, RelA is a functional partner of Hfq that facilitates Hfq-mediated sRNA-mRNA regulation in vivo and induces Hfq hexamerization in vitro. Here, for the first time we show that RelA-mediated Hfq hexamerization requires an initial binding of RNA, preferably sRNA to Hfq monomers. By interacting with a Shine-Dalgarno-like sequence (GGAG) in the sRNA, RelA stabilizes the initially unstable complex of RNA bound-Hfq monomer, enabling the attachment of more Hfq subunits to form a functional hexamer. Overall, our study showing that RNA binding to Hfq monomers is at the heart of RelA-mediated Hfq hexamerization, challenges the previous concept that only Hfq hexamers can bind RNA.

microbiology↗