Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/47221
Title: Effects of subinhibitory concentrations of ceftaroline on Methicillin-Resistant Staphylococcus aureus (MRSA) biofilms
Authors: Lazaro-Diez, Maria
Remuzgo-Martinez, Sara
Rodriguez-Mirones, Cristina
Acosta, Felix 
Icardo, Jose M.
Martinez-Martinez, Luis
Ramos Vivas, Jose 
UNESCO Clasification: 320505 Enfermedades infecciosas
Keywords: In-Vitro
Antibiotic Concentrations
Inhibitory Concentrations
Bactericidal Activity
Cell-Wall, et al
Issue Date: 2016
Journal: PLoS ONE 
Abstract: Ceftaroline (CPT) is a novel cephalosporin with in vitro activity against Staphylococcus aureus. Ceftaroline exhibits a level of binding affinity for PBPs in S. aureus including PBP2a of methicillin-resistant S. aureus (MRSA). The aims of this study were to investigate the morphological, physiological and molecular responses of MRSA clinical strains and MRSA biofilms to sub-MICs (1/4 and 1/16 MIC) of ceftaroline by using transmission, scanning and confocal microscopy. We have also used quantitative Real-Time PCR to study the effect of sub-MICs of ceftaroline on the expression of the staphylococcal icaA, agrA, sarA and sasF genes in MRSA biofilms. In one set of experiments, ceftaroline was able to inhibit biofilm formation in all strains tested at MIC, however, a strain dependent behavior in presence of sub-MICs of ceftaroline was shown. In a second set of experiments, destruction of preformed biofilms by addition of ceftaroline was evaluated. Ceftaroline was able to inhibit biofilm formation at MIC in all strains tested but not at the sub-MICs. Destruction of preformed biofilms was strain dependent because the biofilm formed by a matrix-producing strain was resistant to a challenge with ceftaroline at MIC, whereas in other strains the biofilm was sensitive. At sub-MICs, the impact of ceftaroline on expression of virulence genes was strain-dependent at 1/4 MIC and no correlation between ceftaroline-enhanced biofilm formation and gene regulation was established at 1/16 MIC. Our findings suggest that sub-MICs of ceftaroline enhance bacterial attachment and biofilm formation by some, but not all, MRSA strains and, therefore, stress the importance of maintaining effective bactericidal concentrations of ceftaroline to fight biofilm-MRSA related infections.
URI: http://hdl.handle.net/10553/47221
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0147569
Source: PLoS ONE [ISSN 1932-6203], v. 11 (1), (e0147569) (Enero 2016)
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