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===Introduction>
Transpeptidases (TP), also known as penicillin-binding proteins (PBP),
catalyze the 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 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 methicillinresistant
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 often 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 Students Modeling A Research Topic (SMART)
Team 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.
