The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i>
Methicillin-resistant <i>Staphylococcus aureus</i> infections are a global health problem. New control strategies, including fifth-generation cephalosporins such as ceftaroline, have been developed, however rare sporadic resistance has been reported. Our study aimed to determine whether...
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doaj-f105c9635b0647ff8bc20bac88d62c522021-07-23T13:28:10ZengMDPI AGAntibiotics2079-63822021-07-011082182110.3390/antibiotics10070821The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i>Maite Villanueva0Melanie Roch1Iñigo Lasa2Adriana Renzoni3William L. Kelley4Department of Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1206 Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1206 Geneva, SwitzerlandLaboratory of Microbial Pathogenesis, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), 31008 Pamplona, SpainService of Infectious Diseases, University Hospital and Medical School of Geneva, 1206 Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1206 Geneva, SwitzerlandMethicillin-resistant <i>Staphylococcus aureus</i> infections are a global health problem. New control strategies, including fifth-generation cephalosporins such as ceftaroline, have been developed, however rare sporadic resistance has been reported. Our study aimed to determine whether disruption of two-component environmental signal systems detectably led to enhanced susceptibility to ceftaroline in <i>S. aureus</i> CA-MRSA strain MW2 at sub-MIC concentrations where cells normally continue to grow. A collection of sequential mutants in all fifteen <i>S. aureus</i> non-essential two-component systems (TCS) was first screened for ceftaroline sub-MIC susceptibility, using the spot population analysis profile method. We discovered a role for both ArlRS and VraSR TCS as determinants responsible for MW2 survival in the presence of sub-MIC ceftaroline. Subsequent analysis showed that dual disruption of both <i>arlRS</i> and <i>vraSR</i> resulted in a very strong ceftaroline hypersensitivity phenotype. Genetic complementation analysis confirmed these results and further revealed that <i>arlRS</i> and <i>vraSR</i> likely regulate some common pathway(s) yet to be determined. Our study shows that <i>S. aureus</i> uses particular TCS environmental sensing systems for this type of defense and illustrates the proof of principle that if these TCS were inhibited, the efficacy of certain antibiotics might be considerably enhanced.https://www.mdpi.com/2079-6382/10/7/821ceftaroline<i>Staphylococcus aureus</i>MRSAtwo-component systemsArlRSVraSR |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maite Villanueva Melanie Roch Iñigo Lasa Adriana Renzoni William L. Kelley |
spellingShingle |
Maite Villanueva Melanie Roch Iñigo Lasa Adriana Renzoni William L. Kelley The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i> Antibiotics ceftaroline <i>Staphylococcus aureus</i> MRSA two-component systems ArlRS VraSR |
author_facet |
Maite Villanueva Melanie Roch Iñigo Lasa Adriana Renzoni William L. Kelley |
author_sort |
Maite Villanueva |
title |
The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i> |
title_short |
The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i> |
title_full |
The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i> |
title_fullStr |
The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i> |
title_full_unstemmed |
The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i> |
title_sort |
role of arlrs and vrasr in regulating ceftaroline hypersusceptibility in methicillin-resistant <i>staphylococcus aureus</i> |
publisher |
MDPI AG |
series |
Antibiotics |
issn |
2079-6382 |
publishDate |
2021-07-01 |
description |
Methicillin-resistant <i>Staphylococcus aureus</i> infections are a global health problem. New control strategies, including fifth-generation cephalosporins such as ceftaroline, have been developed, however rare sporadic resistance has been reported. Our study aimed to determine whether disruption of two-component environmental signal systems detectably led to enhanced susceptibility to ceftaroline in <i>S. aureus</i> CA-MRSA strain MW2 at sub-MIC concentrations where cells normally continue to grow. A collection of sequential mutants in all fifteen <i>S. aureus</i> non-essential two-component systems (TCS) was first screened for ceftaroline sub-MIC susceptibility, using the spot population analysis profile method. We discovered a role for both ArlRS and VraSR TCS as determinants responsible for MW2 survival in the presence of sub-MIC ceftaroline. Subsequent analysis showed that dual disruption of both <i>arlRS</i> and <i>vraSR</i> resulted in a very strong ceftaroline hypersensitivity phenotype. Genetic complementation analysis confirmed these results and further revealed that <i>arlRS</i> and <i>vraSR</i> likely regulate some common pathway(s) yet to be determined. Our study shows that <i>S. aureus</i> uses particular TCS environmental sensing systems for this type of defense and illustrates the proof of principle that if these TCS were inhibited, the efficacy of certain antibiotics might be considerably enhanced. |
topic |
ceftaroline <i>Staphylococcus aureus</i> MRSA two-component systems ArlRS VraSR |
url |
https://www.mdpi.com/2079-6382/10/7/821 |
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