OBJECTIVES To characterize the mechanisms responsible for elevated MICs of ceftaroline for methicillin-resistant Staphylococcus aureus (MRSA). METHODS During the 2008 Assessing Worldwide Antimicrobial Resistance Evaluation ('AWARE') surveillance programme, four S. aureus collected from separate patients in Athens, Greece, demonstrated ceftaroline MICs of 4 mg/L. These isolates were clonally r...

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to beta-lactam antibiotics because it expresses penicillin-binding protein 2a (PBP2a), a low-affinity penicillin-binding protein. An investigational broad-spectrum cephalosporin, ceftobiprole (BPR), binds PBP2a with high affinity and is active against MRSA. We hypothesized that BPR resistance could be mediated by mutations in mecA,...

BACKGROUND Formation of biofilm is known to enhance the virulence of methicillin-resistance Staphylococcus aureus (MRSA), which is associated with persistent infections in hospital settings. The biofilm layer essentially forms a protective barrier encapsulating the bacterial colony and thus reduces the effectiveness of chemotherapeutics. We have isolated 9EA-FC-B bioactive fraction from Acalyph...

Ceftaroline, a recently approved β-lactam antibiotic for treatment of infections by methicillin-resistant Staphylococcus aureus (MRSA), is able to inhibit penicillin-binding protein 2a (PBP2a) by triggering an allosteric conformational change that leads to the opening of the active site. The opened active site is now vulnerable to inhibition by a second molecule of ceftaroline, an event that im...

BACKGROUND The inhibition of penicillin-binding protein 2a (PBP2a) is a promising solution in overcoming resistance of methicillin resistance Staphylococcus aureus (MRSA). A potential approach in achieving this is by combining natural product with currently available antibiotics to restore the activity as well as to amplify the therapeutic ability of the drugs. We studied inhibition effects of ...

OBJECTIVES The objectives of this study were to characterize contemporary MRSA isolates and understand the prevalence and impact of sequence variability in PBP2a on ceftaroline susceptibility. METHODS A total of 184 MRSA isolates collected from 28 countries were collected and characterized. RESULTS WT PBP2a proteins were found in MRSA distributed evenly over the ceftaroline MIC range of 0.5...

A number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid inter...

Background: MRSA is a type of MDR bacterium. All around the world, it leads to significant nosocomial and community-acquired diseases. The discovery fresh ideas very important because there are so few effective treatments for infections. PBP2a great candidate development MRSA-specific Mabs. Aim: purpose this study was create murine Mabs against in order enhance laboratory detection possibly tre...

mediate ceftaroline resistance (Table 1). Two isolates (ASARM167 and A38) belonging to ST22 (epidemic MRSA-15) had an E239K substitution in PBP2a. ASARM167 was isolated from a patient with bacteraemia at Cambridge University Hospitals NHS Foundation Trust (CUH) in 2008 and A38 was isolated from a canine wound infection in 2006 treated in Wiltshire, southwest England. 8 Phylogenetic analysis of ...

The expression of penicillin binding protein 2a (PBP2a) is the basis for the broad clinical resistance to the β-lactam antibiotics by methicillin-resistant Staphylococcus aureus (MRSA). The high-molecular mass penicillin binding proteins of bacteria catalyze in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that com...