Sandbox 124: Difference between revisions
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==='''Introduction'''=== | ==='''Introduction'''=== | ||
<scene name='37/372724/Tp_1_in_grey/1'>Transpeptidase</scene>(TP), also known as penicillin-binding proteins (PBP), | <scene name='37/372724/Tp_1_in_grey/1'>Transpeptidase</scene>(Transpeptidases (TP), | ||
also known as penicillin-binding proteins (PBP), catalyze the cross-linking of | |||
synthesis. The natural transpeptidase substrate is the D-Ala-D-Ala | peptidoglycan polymers during bacterial cell wall synthesis. The natural transpeptidase | ||
peptidoglycan side chain terminus. Beta-lactam (β-lactam) antibiotics, which | substrate is the D-Ala-D-Ala peptidoglycan side chain terminus. Beta-lactam (β-lactam) | ||
include penicillins, cephalosporins and carbapenems, bind and irreversibly | antibiotics, which include penicillins, cephalosporins and carbapenems, bind and | ||
inhibit transpeptidases by mimicking the D-Ala-D-Ala substrate, resulting in | irreversibly inhibit transpeptidases by mimicking the D-Ala-D-Ala substrate, resulting | ||
the inhibition of cell wall synthesis and ultimately bacterial cell growth. | 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 | |||
alternative transpeptidase, PBP2a, which is neither bound nor inhibited by β- | neither bound nor inhibited by β-lactams. MRSA isolates are resistant to all β-lactams, and | ||
lactams. MRSA isolates are resistant to all β-lactams, | 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. | |||
antibiotics”, such as vancomycin. Recently, two cephalosporins - ceftobiprole | |||
and ceftaroline - that bind and inhibit PBP2a have been developed. | |||
'''Cell Wall Synthesis''' | '''Cell Wall Synthesis''' |