High-Level Resistance of Staphylococcus aureus to ß-Lactam Antibiotics Mediated by Penicillin-Binding Protein 4 (PBP4).
Antimicrob Agents Chemother
; 61(6)2017 06.
Article
en En
| MEDLINE
| ID: mdl-28373193
ABSTRACT
Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of Staphylococcus aureus, has been implicated in low-level resistance to ß-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to ß-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of S. aureus These mutations did not appreciably alter the ß-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity. The pbp4 promoter mutation of CRB was associated with greatly increased amounts of PBP4 in membranes compared to those in the COLnex parent. Replacement of the native promoter of COLnex with the mutant promoter of CRB resulted in increased amounts of PBP4 in membranes and a highly cross-linked cell wall. PBP4 can be repurposed to provide essential transpeptidase activity in vivo and confer high-level resistance to ß-lactam antibiotics, such as ceftobiprole and ceftaroline.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
/
Beta-Lactamas
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos