Journal
NUCLEIC ACIDS RESEARCH
Volume 50, Issue 15, Pages 8529-8546Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac648
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Funding
- CNRS/Universite Paris-Saclay
- INSERM/Universite Rennes 1
- 'Agence Nationale de la Recherche' (ANR) [ANR-15-CE12-0003-01]
- 'Fondation pour la Recherche Medicale' (FRM) [DBF20160635724]
- ANR [ANR-19-CE45-0023-02, ANR-19-CE12-0006-01]
- CNRS
- Universite de Paris
- 'Consejo Nacional de Ciencia y Tecnologia' (CONACyT) [ANRS-A02019-2 ECTZ108689]
- Agence Nationale de la Recherche contre le SIDA fellowship [ANRS-A02019-2 ECTZ108689]
- Agence Nationale de la Recherche (ANR) [ANR-19-CE12-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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Staphylococcus aureus adjusts its metabolism to cope with iron deprivation within the host, and the small non-coding RNA IsrR plays an important role in this process. IsrR down-regulates the translation of enzymes involved in anaerobic nitrate respiration during iron starvation. Additionally, IsrR is required for the full lethality of S. aureus in a mouse septicemia model.
Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.
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