Ceftaroline resistance by clone-specific polymorphism in penicillin-binding protein 2a of methicillin-resistant staphylococcus aureus

Hyukmin Lee, Eun Jeong Yoon, Dokyun Kim, Jung Wook Kim, Kwang Jun Lee, Hyun Soo Kim, Young Ree Kim, Jong Hee Shin, Jeong Hwan Shin, Kyeong Seob Shin, Young Ah Kim, Young Uh, Seok Hoon Jeong

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Abstract

A total of 281 nonduplicated Staphylococcus aureus blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant S. aureus (MRSA). Cefoxitin-disk diffusion tests and the mecA gene PCR revealed that 56.6% (159/281) of the S. aureus isolates were MRSA, and most belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159) were nonsusceptible to ceftaroline (MIC 2 mg/liter), whereas all of the methicillin-susceptible S. aureus isolates were susceptible to the drug. Eight amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four (L357I, E447K, I563T, and S649A) in the penicillin-binding domain (PBD) and four (N104K, V117I, N146K, and A228V) in the non-PBD (nPBD) of PBP2a, were associated with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted in the elevation of ceftaroline MICs: one substitution at 1 to 2 mg/liter, two or three substitutions at 2 to 4 mg/liter, and five substitutions at 4 or 16 mg/liter. Ceftaroline resistance in MRSA might be the result of clone-specific PBP2a polymorphism, along with substitutions both in PBD and nPBD, and the elevated ceftaroline MICs were associated with the substitution sites and accumulation of substitutions.

Original languageEnglish
Article numbere00485-18
JournalAntimicrobial agents and chemotherapy
Volume62
Issue number9
DOIs
Publication statusPublished - 2018 Sep

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Lee, H., Yoon, E. J., Kim, D., Kim, J. W., Lee, K. J., Kim, H. S., Kim, Y. R., Shin, J. H., Shin, J. H., Shin, K. S., Kim, Y. A., Uh, Y., & Jeong, S. H. (2018). Ceftaroline resistance by clone-specific polymorphism in penicillin-binding protein 2a of methicillin-resistant staphylococcus aureus. Antimicrobial agents and chemotherapy, 62(9), [e00485-18]. https://doi.org/10.1128/AAC.00485-18