Staphylococcus aureus susceptibility to complestatin and corbomycin depends on the VraSR two-component system
| dc.contributor.author | Gómez Arrebola, Carmen | |
| dc.contributor.author | Hernández, Sara B. | |
| dc.contributor.author | Culp, Elizabeth J. | |
| dc.contributor.author | Wright, Gerard D. | |
| dc.contributor.author | Solano Goñi, Cristina | |
| dc.contributor.author | Cava, Felipe | |
| dc.contributor.author | Lasa Uzcudun, Íñigo | |
| dc.contributor.department | Ciencias de la Salud | es_ES |
| dc.contributor.department | Osasun Zientziak | eu |
| dc.contributor.funder | Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa | es |
| dc.date.accessioned | 2023-09-13T11:41:49Z | |
| dc.date.available | 2023-09-13T11:41:49Z | |
| dc.date.issued | 2023 | |
| dc.date.updated | 2023-09-13T11:28:32Z | |
| dc.description.abstract | The overuse of antibiotics in humans and livestock has driven the emergence and spread of antimicrobial resistance and has therefore prompted research on the discovery of novel antibiotics. Complestatin (Cm) and corbomycin (Cb) are glycopeptide antibiotics with an unprecedented mechanism of action that is active even against methicillin-resistant and daptomycin-resistant Staphylococcus aureus. They bind to peptidoglycan and block the activity of peptidoglycan hydrolases required for remodeling the cell wall during growth. Bacterial signaling through two-component transduction systems (TCSs) has been associated with the development of S. aureus antimicrobial resistance. However, the role of TCSs in S. aureus susceptibility to Cm and Cb has not been previously addressed. In this study, we determined that, among all 16 S. aureus TCSs, VraSR is the only one controlling the susceptibility to Cm and Cb. Deletion of vraSR increased bacterial susceptibility to both antibiotics. Epistasis analysis with members of the vraSR regulon revealed that deletion of spdC, which encodes a membrane protein that scaffolds SagB for cleavage of peptidoglycan strands to achieve physiological length, in the vraSR mutant restored Cm and Cb susceptibility to wild-type levels. Moreover, deletion of either spdC or sagB in the wild-type strain increased resistance to both antibiotics. Further analyses revealed a significant rise in the relative amount of peptidoglycan and its total degree of cross-linkage in ΔspdC and ΔsagB mutants compared to the wild-type strain, suggesting that these changes in the cell wall provide resistance to the damaging effect of Cm and Cb. | en |
| dc.description.sponsorship | This work was financially supported by the Spanish Ministry of Science and Innovation grant PID2020-113494RB-I00 to I.L. (Agencia Española de Investigación/Fondo Europeo de Desarrollo Regional, European Union) and a Canadian Institutes of Health Research grant (FRN-148463; to G.D.W.). C.G.A. was supported by a predoctoral contract from the Public University of Navarra. Research in the Cava lab was supported by The Swedish Research Council (VR), The Knut and Alice Wallenberg Foundation (KAW), The Laboratory of Molecular Infection Medicine Sweden (MIMS) and The Kempe Foundation. | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Gómez-Arrebola, C., Hernandez, S. B., Culp, E. J., Wright, G. D., Solano, C., Cava, F., & Lasa, I. (2023). Staphylococcus aureus susceptibility to complestatin and corbomycin depends on the vrasr two-component system. Microbiology Spectrum, e00370-23. https://doi.org/10.1128/spectrum.00370-23 | en |
| dc.identifier.doi | 10.1128/spectrum.00370-23 | |
| dc.identifier.issn | 2165-0497 | |
| dc.identifier.uri | https://academica-e.unavarra.es/handle/2454/46330 | |
| dc.language.iso | eng | en |
| dc.publisher | American Society for Microbiology | en |
| dc.relation.ispartof | Microbiology Spectrum, (2023), 1-16 | en |
| dc.relation.projectID | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113494RB-I00/ES/ | |
| dc.relation.publisherversion | https://doi.org/10.1128/spectrum.00370-23 | |
| dc.rights | © 2023 Gómez-Arrebola et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. | en |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | Staphylococcus aureus | en |
| dc.subject | Two-component system | en |
| dc.subject | VraSR | en |
| dc.subject | Complestatin | en |
| dc.subject | Corbomycin | en |
| dc.subject | Autolysins | en |
| dc.title | Staphylococcus aureus susceptibility to complestatin and corbomycin depends on the VraSR two-component system | en |
| dc.type | info:eu-repo/semantics/article | |
| dc.type.version | info:eu-repo/semantics/publishedVersion | |
| dspace.entity.type | Publication | |
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