Sandbox 126
From Proteopedia
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| - | Transpeptidase (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 (B-Lactam) antibiotics, which include penicillins, cephalosporins and carbapenems, bind and irreversibly inhibit transpeptidases by mimicking the D-Ala-D-Ala moiety, resulting in the inhibition of cell wall synthesis and ultimately bacterial cell growth. Overuse and misuse of beta-lactams has led to the generation of methicillin-resistant ''Staphylococcus aureus'' (MRSA) isolates that have acquired an alternative transpeptidase, PBP2a, which is compromised in its ability to react with beta-lactams. MRSA isolates are resistant to all beta-lactams, can be hospital- or community-acquired, and are often the cause of significant morbidity and mortality. Futhermore, they are often only susceptible to so-called "last resort antibiotics", such as vancomycin. Recently, two broad range cephalosporins, ceftobiprole and ceftaroline, that bind and inhibit PBP2a have been developed. | + | ==='''Introduction'''=== |
| + | Transpeptidase (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 (B-Lactam) antibiotics, which include penicillins, cephalosporins and carbapenems, bind and irreversibly inhibit transpeptidases by mimicking the D-Ala-D-Ala moiety, resulting in the inhibition of cell wall synthesis and ultimately bacterial cell growth. Overuse and misuse of beta-lactams has led to the generation of methicillin-resistant ''Staphylococcus aureus'' (MRSA) isolates that have acquired an alternative transpeptidase, PBP2a, which is compromised in its ability to react with beta-lactams. MRSA isolates are resistant to all beta-lactams, can be hospital- or community-acquired, and are often the cause of significant morbidity and mortality. Futhermore, they are often only susceptible to so-called "last resort antibiotics", such as vancomycin. Recently, two broad range cephalosporins, ceftobiprole and ceftaroline, that bind and inhibit PBP2a have been developed. | ||
Revision as of 18:54, 7 July 2014
Introduction
Transpeptidase (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 (B-Lactam) antibiotics, which include penicillins, cephalosporins and carbapenems, bind and irreversibly inhibit transpeptidases by mimicking the D-Ala-D-Ala moiety, resulting in the inhibition of cell wall synthesis and ultimately bacterial cell growth. Overuse and misuse of beta-lactams has led to the generation of methicillin-resistant Staphylococcus aureus (MRSA) isolates that have acquired an alternative transpeptidase, PBP2a, which is compromised in its ability to react with beta-lactams. MRSA isolates are resistant to all beta-lactams, can be hospital- or community-acquired, and are often the cause of significant morbidity and mortality. Futhermore, they are often only susceptible to so-called "last resort antibiotics", such as vancomycin. Recently, two broad range cephalosporins, ceftobiprole and ceftaroline, that bind and inhibit PBP2a have been developed.
