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Updated: Apr 25, 2026
Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant Staphylococcus aureus
S Wesley Long1, Randall J Olsen1, Shrenik C Mehta2
1Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, Texas, USA.
Abstract:
Ceftaroline is the first member of a novel class of cephalosporins approved for use in the United States. Although prior studies have identified eight ceftaroline-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolates in Europe and Asia with MICs ranging from 4 to 8 mg/liter, high-level resistance to ceftaroline (>32 mg/liter) has not been described in MRSA strains isolated in the United States. We isolated a ceftaroline-resistant (MIC > 32 mg/liter) MRSA strain from the blood of a cystic fibrosis patient and five MRSA strains from the respiratory tract of this patient. Whole-genome sequencing identified two amino acid-altering mutations uniquely present in the ceftaroline-binding pocket of the transpeptidase region of penicillin-binding protein 2a (PBP2a) in ceftaroline-resistant isolates. Biochemical analyses and the study of isogenic mutant strains confirmed that these changes caused ceftaroline resistance. Thus, we identified the molecular mechanism of ceftaroline resistance in the first MRSA strain with high-level ceftaroline resistance isolated in the United States.
Insights
Ceftaroline resistance in MRSA was identified in the US for the first time. Two mutations in penicillin-binding protein 2a (PBP2a) were found to cause high-level ceftaroline resistance in methicillin-resistant Staphylococcus aureus.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Ceftaroline is a novel cephalosporin antibiotic used to treat infections.
- Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen.
- Previous reports documented ceftaroline resistance in MRSA outside the United States.
Observation:
- A ceftaroline-resistant MRSA strain (MIC > 32 mg/liter) was isolated from a cystic fibrosis patient in the US.
- Multiple MRSA strains with ceftaroline resistance were recovered from the same patient.
Findings:
- Whole-genome sequencing revealed two specific amino acid mutations in the PBP2a binding pocket.
- These mutations in penicillin-binding protein 2a (PBP2a) were uniquely present in resistant isolates.
- Biochemical analysis confirmed these PBP2a mutations confer high-level ceftaroline resistance.
Implications:
- Identifies the molecular mechanism for high-level ceftaroline resistance in US MRSA.
- Provides critical information for understanding and combating antibiotic resistance.
- Informs clinical treatment strategies for MRSA infections.
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