Penicillins bacterial cell wall synthesis inhibited

The mechanism of antibacterial activity is through inhibition of gram-positive bacterial cell-wall synthesis thus, the penicillins are most effective against actively multiplying organisms. Because mammalian cells do not have a definitive cell-wall stmcture as do bacteria, the mammalian toxicity of the penicillins is low. Allergic phenomena in patients following sensitization may occur. 

In general, penicillins exert thek biological effect, as do the other -lactams, by inhibiting the synthesis of essential structural components of the bacterial cell wall. These components are absent in mammalian cells so that inhibition of the synthesis of the bacterial cell wall stmcture occurs with Htde or no effect on mammalian cell metaboHsm. Additionally, penicillins tend to be kreversible inhibitors of bacterial cell-wall synthesis and are generally bactericidal at concentrations close to thek bacteriostatic levels. Consequently penicillins have become widely used for the treatment of bacterial infections and are regarded as one of the safest and most efficacious classes of antibiotics. 

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... 

Beta-lactam antibiotics are a second great class of antibacterials penicillins, cephalosporins, carbapenems, and monobactams. They act by inhibiting bacterial cell wall synthesis. 

Pharmacology Aztreonam, a synthetic bactericidal antibiotic, is the first of a class identified as monobactams. The monobactams have a monocyclic -lactam nucleus. Aztreonam s bactericidal action results from the inhibition of bacterial cell wall synthesis because of a high affinity of aztreonam for penicillin-binding protein 3 (PBP3). 

Mechanism of Action A penicillin that inhibits bacterial cell wall synthesis. Therapeutic Effect Bactericidal in susceptible microorganisms. 

Mechanism of Action A carbapenem that binds to penicillin-binding proteins and inhibits bacterial cell wall synthesis. Therapeutic Effect Produces bacterial cell death. Pharmacohinetics After IV administration, widely distributed into tissues and body fluids, including CSF. Protein binding 2%. Primarily excreted unchanged in urine. Removed by hemodialysis. Half-life 1 hr. 

Mechanism of Action A penicillin that acts as a bactericidal in susceptible microorganisms. Therapeutic Effect Inhibits bacterial cell wall synthesis. Bactericidal. Pharmacokinetics Poorly absorbed from gastrointestinal (GI) tract. Protein binding 87%-90%. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life 10.5-1 hr (half-life increased with imparted renal function). 

Mechanism of Action Penicillins bind to bacterial cell wall, inhibiting bacterial cell wall synthesis. Therapeutic Effect Inhibits bacterial cell wall synthesis. Beta-lacta-mase inhibitors inhibit the action of bacterial beta-lactamase. Therapeutic Effect Protects the penicillin from enzymatic degradation. 

The bacterial cell wall is a rigid outer layer that completely surrounds the cytoplasmic membrane. Penicillin and other betalactam antibiotics inhibit bacterial growth by interfering with a specific step in bacterial cell wall synthesis. Penicillins are classified as in table 9.3.1. 

Penicillin G Prevents bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases Rapid bactericidal activity against susceptible bacteria Streptococcal infections, meningococcal infections, neurosyphilis IV administration rapid renal clearance (half-life 30 min, so requires frequent dosing (every 4 h) Toxicity Immediate hypersensitivity, rash, seizures... 

Examples of enzyme inhibitors that can be used as drugs Enzyme inhibitors can be used as drugs, inhibiting either intracellular or extracellular reactions. For example, the p-lactam antibiotics, such as penicillin and amoxicillin, act by inhibiting one or more of the enzymes of bacterial cell wall synthesis. 

Unfortunately, there are few pure examples of true selective toxicity. Perhaps the best is penicillin. The therapeutic specificity of this antibiotic is based upon the qualitative difference between bacterial cell wall synthesis and mammalian cell membrane synthesis. Synthesis of the former can be inhibited by penicillin while the latter is unaffected. Thus, penicillin is one of the few examples of a drug that can actually cure an illness. A similar example involves the sulfa drugs, which interfere with the synthesis of folic acid, used in nucleic acid formation, in bacteria. While bacteria must synthesize their own folic acid, mammalian cells utilize dietary, preformed folic acid and are not susceptible to interference with its formation. 

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. 

Further observations were published concerning the mechanism of action of the penicillins.Data support the concept that the P-lactam antibiotics inhibit a transpeptidase essential for a cross-linking reaction in bacterial cell-wall synthesis. Transpeptidase derived from cell-free systems of E. coli, like that from aureus, is inactivated by penicillins. Thus, the possession of cellular permeability barriers in addition to P-lactamase productive capacity apparently tends to protect greun-negative bacteria from lethal attack by P-lactam antibiotics.33... 

Inhibition of bacterial cell-wall synthesis Penicillins, cephalosporins, imipenem/meropenem, aztreonam, vancomycin... 

Cephalosporins and cephamycins inhibit bacterial cell wall synthesis in a manner similar to that of penicillin. 

Erythromycin. Erythromycin and the other macrolide antibiotics bind to the 508 ribosomal subunit of bacteria near the binding site for chloramphenicol. They prevent the translocation step, the movement of the peptidyl-tRNA from the A to the P site on the ribosome. Because the side effects are less severe and more readily reversible than those of many other antibiotics, the macrolides are often used to treat infections in persons who are allergic to penicillin, an antibiotic that inhibits bacterial cell wall synthesis. However, bacterial resistance to erythromycin is increasing. ThCTefore, its close relative, clarithromycin, is often used. 

Penicillins and cephalosporins (Figure 43-1) are the major antibiotics that inhibit bacterial cell wall synthesis. They are called beta-lactams because of the unusual four-member ring that is common to... 

C. Mechanisms of Action and Resistance Cephalosporins bind to PBPs on bacterial cell membranes to inhibit bacterial cell wall synthesis by mechanisms similar to those of the penicillins. Cephalosporins are bactericidal against susceptible organisms. 

Figure 7.10 Bacterial cell wall synthesis. 1) Alanine molecules are added to a carbohydrate tripeptide to form a "T" shaped cell wall precursor. This reaction is inhibited by D-cycloserine. 2) The precursor is transported across the plasma membrane by a carrier. Vancomycin inhibits the transport process. 3) The transporter is recycled to the inside of the cell to carry other precursors. Bacitracin inhibits this step. 4) The precursor is linked to the existing cell wall structure by transpeptidase. Penicillins, cephalosporins, imipenem and aztreonam inhibit the transpeptidase. Transpeptidase is one of several penicillin binding proteins and is not the only site of penicillin action.

The inhibition of bacterial cell wall synthesis by penicillin is a classic example of a medically significant inhibition of an enzymatic reaction. Which of the following statements about the inhibition of glycopeptide transpeptidase by penicillin is true ... 

Penicillins, cephalosporins, tetracyclines, acrinomvdns These are examples of classes of antibiotics each from a microorganism producing c) otoxic agents. The first three classes are selectively c) otoxic to bacteria, and the fourth cytotoxic to mammalian cancer cells, unfortunately with poor selective toxicity. The penicillins and cephalosporins inhibit bacterial cell wall synthesis, and tetracyclines selectively block protein synthesis at the bacterial ribosome. The actinomycins intercalate in a relative nonselective manner the... 

The generally accepted explanation is that bactericides such as the penicillins, which inhibit bacterial cell wall synthesis, require cells to be actively growing and dividing to be maximally effeetive, a situation that will not occur in the presence of bacteriostatic antibacterials, sueh as the tetracyclines. 

Recent work on the structure and biosynthesis of bacterial cell walls has given some indication of the way in which the crosslinked polysaccharide components are formed. There are several justifications for including here a brief account of work in this field. Firstly, certain antibiotics (e.g. the penicillins, bacitracin A, novabiocin) are known specifically to inhibit bacterial cell-wall synthesis. If, as seems likely, the inhibition is of an enzyme-catalysed reaction, a knowledge of the particular substrates involved might lead to the design of more powerful bactericidal agents. Secondly, the particular type of cell... 

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