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Peer-reviewedCC BY 4.0The EMBO Journal

The miR-744-5p/connexin 43 axis modulates Salmonella-containing vacuole association with the Golgi network

  • Jane Dias1,2
  • Caio Haddad Franco1,2,3
  • Laura Maria Alcantara1,2,3
  • Susana Costa1,2
  • Miguel Mano2,4
  • Ana Eulalio1,5
5 affiliations
  1. 1RNA & Infection Laboratory, Center for Neuroscience and Cell Biology (CNC-UC), Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
  2. 2Functional Genomics and RNA-based Therapeutics Laboratory, Center for Neuroscience and Cell Biology (CNC-UC), Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
  3. 3Collaborative Laboratory to Foster Translation and Drug Discovery (AccelBio), Cantanhede, Portugal
  4. 4School of Cardiovascular and Metabolic Medicine & Sciences, King’s College London, London, UK
  5. 5Centre for Bacterial Resistance Biology (CBRB), Department of Life Sciences, Imperial College London, London, UK
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Abstract

MicroRNAs are increasingly recognised as important regulators of host–pathogen interactions. Using a large-scale functional screening approach, we identified miR-744-5p as a strong inhibitor of Salmonella infection. Time-course analyses in epithelial cells revealed that miR-744-5p moderately restricts early infection but exerts a much stronger inhibitory effect on late intracellular replication. This activity is conserved across Salmonella strains of distinct sequence types, whereas inhibition of Shigella flexneri is limited to early infection stages. Integrated transcriptomic analyses identified connexin 43 as a functionally relevant miR-744-5p target. Connexin 43 expression is strongly upregulated during Salmonella infection, and functional studies demonstrated that connexin 43 depletion selectively impaired late-stage intracellular replication, while CRISPRa-mediated connexin 43 upregulation enhanced bacterial proliferation. Notably, this function was independent of the canonical gap junction intercellular communication. Mechanistically, connexin 43 is required to maintain Golgi network organisation, enabling proper positioning of the Salmonella-containing vacuole. Thus, infection-induced downregulation of miR-744-5p promotes connexin 43 expression to support the formation of a permissive vacuolar replicative niche, revealing an unanticipated role for connexin 43 in Golgi homeostasis.

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Cite

BibTeXRIS
BibTeX
@article{dias2026mir7445pconnexin,
  title = {{The miR-744-5p/connexin 43 axis modulates Salmonella-containing vacuole association with the Golgi network}},
  author = {Jane Dias and Caio Haddad Franco and Laura Maria Alcantara and Susana Costa and Miguel Mano and Ana Eulalio},
  journal = {The EMBO Journal},
  year = {2026},
  month = oct,
  doi = {10.1038/s44318-026-00929-3},
  url = {https://doi.org/10.1038/s44318-026-00929-3},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The miR-744-5p/connexin 43 axis modulates Salmonella-containing vacuole association with the Golgi network
AU  - Jane Dias
AU  - Caio Haddad Franco
AU  - Laura Maria Alcantara
AU  - Susana Costa
AU  - Miguel Mano
AU  - Ana Eulalio
PY  - 2026
DA  - 2026/10/10
JO  - The EMBO Journal
DO  - 10.1038/s44318-026-00929-3
UR  - https://doi.org/10.1038/s44318-026-00929-3
AB  - MicroRNAs are increasingly recognised as important regulators of host–pathogen interactions. Using a large-scale functional screening approach, we identified miR-744-5p as a strong inhibitor of Salmonella infection. Time-course analyses in epithelial cells revealed that miR-744-5p moderately restricts early infection but exerts a much stronger inhibitory effect on late intracellular replication. This activity is conserved across Salmonella strains of distinct sequence types, whereas inhibition of Shigella flexneri is limited to early infection stages. Integrated transcriptomic analyses identified connexin 43 as a functionally relevant miR-744-5p target. Connexin 43 expression is strongly upregulated during Salmonella infection, and functional studies demonstrated that connexin 43 depletion selectively impaired late-stage intracellular replication, while CRISPRa-mediated connexin 43 upregulation enhanced bacterial proliferation. Notably, this function was independent of the canonical gap junction intercellular communication. Mechanistically, connexin 43 is required to maintain Golgi network organisation, enabling proper positioning of the Salmonella-containing vacuole. Thus, infection-induced downregulation of miR-744-5p promotes connexin 43 expression to support the formation of a permissive vacuolar replicative niche, revealing an unanticipated role for connexin 43 in Golgi homeostasis.
SN  - 0261-4189
SN  - 1460-2075
ER  -