Penicillin peptidoglycan inhibition

Figure 8. Penicillin (right) and the normal substrate for the enzyme that is inhibited by penicillin. Peptidoglycan is normally cross-linked in the bacterial cell wall to create a tough lattice of covalent bonds. However, if penicillin binds to and inhibits the enzymes needed for the cross-linking process, the bacteria will not survive.

Mode of action Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls bacteria usually lyse from ongoing autolytic enzyme activity... 

When grouped on the basis of similarities in their chemical structure, most antibiotics fall into the categories listed in Table 1.17. S-Lactams, which include penicillins and cephalosporins, exhibit a characteristic /i-lactam core ring structure (a four-atom cyclic amide) (Figure 1.14). They induce their bacteriocidal activity by inhibiting the synthesis of peptidoglycan, an essential component of the bacterial cell wall. 

All -lactam antibiotics are bactericidal. They interfere with the synthesis of the bacterial wall by inhibiting the bacterial ftanspeptidase enzymes essential for the construction of peptidoglycan of the wall. Some -lactams may be inactivated by the -lactamases (penicillinases) produced by bacteria and, thus, the activity of both penicillins and cephalosporins can be determined by their ability to withstand the destructive action of -lactamases also produced by the organism for its optimal protection. Bacterial resistance caused by -lactamase production... 

Mode of Action. Penicillins exeit their antibacterial effect by inhibiting the high molecular weight penicillin-binding proteins (PBPs) that are implicated in the final stages of peptidoglycan synthesis. 

The cephalosporin drugs, which are also classified as beta-lactam antibiotics, exert their bactericidal effects in a manner similar to that of the penicillins (inhibition of PBPs, resulting in inadequate peptidoglycan production).56 Generally, the cephalosporins serve as alternative agents to penicillins if the penicillin drugs are ineffective or poorly tolerated by the patient. Cephalosporins may also be the drugs of choice in certain types of urinary tract infections (see Tables 33-5). 

Inhibition of transpeptidase Some PBPs catalyze formation of the cross-linkages between peptidoglycan chains. Penicillins inhibit this transpeptidase-catalyzed reaction, thus hindering the formation of crosslinks essential for cell wall integrity. As a result of this blockade of cell wall synthesis, the Park peptide , UDP-acetylmuramyl-L-Ala-D-GIn-L-Lys-D-Ala-D-Ala, accumulates. 

Mode of action. Penicillins act by inhibiting the enzymes (Penicillin Binding Proteins, PBPs) involved in the crosslinking of the peptidoglycan layer of the cell wall which protects the bacterium from its environment incapable of withstanding... 

Selective inhibition of bacterial cell wall synthesis (penicillins, cephalosporins, bacitracin, vancomycin). Following attachment to receptors (penicillinbinding proteins), p-lactam antibiotics inhibit transpeptidation enzymes and thereby block the final stage of peptidoglycan sysnthesis. This action is followed by inactivation of an inhibitor of autolytic enzymes in the bacterial cell wall. Bacitracin and vancomycin inhibit early stages of peptidoglycan synthesis. 

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