Sandbox 124

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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.