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RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures

Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus au...

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Autores principales: Catalan-Moreno, Arancha, Cela, Marta, Menendez-Gil, Pilar, Irurzun, Naiara, Caballero, Carlos J, Caldelari, Isabelle, Toledo-Arana, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034633/
https://www.ncbi.nlm.nih.gov/pubmed/33660769
http://dx.doi.org/10.1093/nar/gkab117
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author Catalan-Moreno, Arancha
Cela, Marta
Menendez-Gil, Pilar
Irurzun, Naiara
Caballero, Carlos J
Caldelari, Isabelle
Toledo-Arana, Alejandro
author_facet Catalan-Moreno, Arancha
Cela, Marta
Menendez-Gil, Pilar
Irurzun, Naiara
Caballero, Carlos J
Caldelari, Isabelle
Toledo-Arana, Alejandro
author_sort Catalan-Moreno, Arancha
collection PubMed
description Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment.
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spelling pubmed-80346332021-04-14 RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures Catalan-Moreno, Arancha Cela, Marta Menendez-Gil, Pilar Irurzun, Naiara Caballero, Carlos J Caldelari, Isabelle Toledo-Arana, Alejandro Nucleic Acids Res Molecular Biology Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment. Oxford University Press 2021-02-28 /pmc/articles/PMC8034633/ /pubmed/33660769 http://dx.doi.org/10.1093/nar/gkab117 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Catalan-Moreno, Arancha
Cela, Marta
Menendez-Gil, Pilar
Irurzun, Naiara
Caballero, Carlos J
Caldelari, Isabelle
Toledo-Arana, Alejandro
RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures
title RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures
title_full RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures
title_fullStr RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures
title_full_unstemmed RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures
title_short RNA thermoswitches modulate Staphylococcus aureus adaptation to ambient temperatures
title_sort rna thermoswitches modulate staphylococcus aureus adaptation to ambient temperatures
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034633/
https://www.ncbi.nlm.nih.gov/pubmed/33660769
http://dx.doi.org/10.1093/nar/gkab117
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