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Physical Model of the Staphylococcus aureus Transpeptidase PBP2a in Complex with an Anti‐Methicillin‐Resistant Staphylococcus aureus Cephalosporin
Author(s) -
Assad Fatima,
Bhiki K.,
Eusebio D.,
Flores E.,
Paulino M.,
Ramirez A.,
Ramirez H.,
Valentin T.,
Zaman M.,
Sussman J. L.,
Lovering A. L.,
Westblade L. F.,
Granberry A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb172
Subject(s) - peptidoglycan , penicillin binding proteins , cephalosporin , staphylococcus aureus , microbiology and biotechnology , antibiotics , penicillin , chemistry , bacterial cell structure , cell wall , bacteria , biology , biochemistry , genetics
Transpeptidases, also known as penicillin‐binding proteins (PBP), catalyze cross‐linking of peptidoglycan polymers during bacterial cell wall synthesis. The natural transpeptidase substrate is the D‐Ala‐ D‐Ala peptidoglycan side chain terminus. Beta‐lactam (β‐lactam) antibiotics, which include the monobactams, penicillins, cephalosporins and carbapenems, bind and irreversibly inhibit transpeptidases by mimicking the D‐Ala‐D‐Ala substrate, resulting in the inhibition of cell wall synthesis and ultimately bacterial cell growth. Overuse and misuse of β‐lactams has led to the generation of methicillin‐resistant Staphylococcus aureus (MRSA) isolates that have acquired an alternative transpeptidase, PBP2a, which is neither bound nor inhibited by β‐lactams. MRSA isolates are resistant to all β‐lactams, can be hospital‐ or community‐acquired, and are the cause of significant morbidity and mortality. Furthermore, they are often only susceptible to “last resort antibiotics”, such as vancomycin. Recently, two cephalosporins ‐ ceftobiprole and ceftaroline ‐ that bind and inhibit PBP2a have been developed. The Hostos‐Lincoln Academy SMART Team (Students Modeling A Research Topic) has generated a model of the PBP2a/ceftobiprole complex (PDB 4DKI ) using 3D printing technology to illustrate the mechanism of action of ceftobiprole. Supported by a grant from the Camille and Henry Dreyfus Foundation