PBP2a mutations causing high-level Ceftaroline resistance in clinical 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.