Bacterial Cell Wall Synthesis

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. 

A book (1) and several general reviews (2—4) on P-lactamases have been pubUshed. Based on sequence data, it has been suggested that P-lactamases evolved from the enzymes involved in bacterial cell wall synthesis (5—7). 

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. 

This insertion is accomplished by an enzyme called transpeptidase. -Lactam antibiotics function as substrates for the transpeptidase, thereby establishing selective inhibition of bacterial cell wall synthesis. The structural similarity between -lactam antibiotics and the alanylalanine unit is remarkable as can be seen in Figure 6.8. 

Like penicillins, cephalosporins are (3-lactam antibiotics and interfere with bacterial cell wall synthesis. A very large number of cephalosporins are available for clinical use. They differ in their route of administration and clinical use. 

Vancomycin (Vancocin) acts against susceptible gram-positive bacteria by inhibiting bacterial cell wall synthesis and increasing cell wall permeability. This drug is used in the treatment of serious gram-positive infections that do not respond to treatment with other anti-infectives. It also may be used in treating anti-infective-associated pseudomembranous colitis caused by Clostridium difficile. 

Most aiititubercular drag s are bacteriostatic (slow or retard the growth of bacteria) against the M. tuberculosis bacillus. These dm usually act to inhibit bacterial cell wall synthesis, which slows the multiplication rate of the bacteria. Only isoniazid is bactericidal, with rifampin and streptomycin having some bactericidal activity. 

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... 

Inhibit bacterial cell-wall synthesis by Streptococci, meningococci,... 

J. L. Strominger, Enzymatic Reactions in Bacterial Cell Wall Synthesis Sensitive to Penicillins, Cephalosporins, and Other Antibacterial Agents , Antibiotics 1967, 1, 705-713. 

P-Lactam antibiotics inhibit bacterial cell wall synthesis... 

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

Biapenem (14 Omegacin ) Thienamycin (11) Carbapenem- type p-lactum NP-derived Microbial Antibacterial Inhibits bacterial cell wall synthesis 201-210... 

Bacterial cell wall synthesis inhibitor, d-ALANINE-d-ALANINE LIGASE BACTERIAL LEADER PEPTIDASE I Bacterial reorientation,... 

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). 

The glycopeptides include vancomycin and teico-planin. They are bactericidal antibiotics. Their mechanism of action is based on inhibition of bacterial cell-wall synthesis by blocking the polymerization of glycopeptides. They do not act from within the peptidoglycan layer, as the beta-lactam antibiotics do, but intracellularly. The indications are mainly restricted to the management of severe or resistant staphylococcal infections, especially those caused by coagulase negative staphylococcal species such as S. epidermidis. 

B. Overproduction (A) of PABA is one of the resistance mechanisms of sulfonamides. Changes in the synthesis of DNA gyrases (B) is a well-described mechanism for quinolone resistance. Plasmid-mediated resistance (C) does not occur with quinolones. An active efflux system for transport of drug out of the cell has been described for quinolone resistance, but it is not plasmid mediated. Inhibition of structural blocks (D) in bacterial cell wall synthesis is a basic mechanism of action of p-lactam antibiotics. Inhibition of folic acid synthesis (E) by blocking different steps is the basic mechanism of action of sulfonamides. 

A number of antibiotics produced by fungi of the genus Cephalosporium have been identified. These antibiotics called cephalosporins contain, in common with the penicillins, a p-lactam ring. In addition to the numerous penicillins and cephalosporins in use, three other classes of p-lactam antibiotics are available for clinical use. These are the carbapenems, the carbacephems, and the monobactams. All 3-lactam antibiotics have the same bactericidal mechanism of action. They block a critical step in bacterial cell wall synthesis. 

L Many antibiotics appear to have as their mechanism of action the capacity to inhibit bacterial cell wall synthesis. This does NOT appear to be a mechanism of... 

L A. The aminoglycosides appear to act by binding to various sites on bacterial SOS ribosomal subunits and disrupting the initiation of protein synthesis. The other agents appear to have the capacity to directly inhibit bacterial cell-wall synthesis. 

D-alanine that is involved in bacterial cell wall synthesis. Cycloserine is inhibitory to M. tuberculosis and active against Escherichia coli, S. aureus, and Enterococcus, Nocardia, and Chlamydia spp. It is used in the treatment of MDR tuberculosis and is useful in renal tuberculosis, since most of the drug is excreted unchanged in the urine. 

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

Mechanism of Action Ampicillin inhibits bacterial cell wall synthesis, while sulbactam inhibits bacterial beta-lactamase. Therapeutic Effect Ampicillin is bactericidal in susceptible microorganisms. Sulbactam protects ampicillin from enzymaticdegrada-tion... 

Mechanism of Action Anantibioticthatinterfereswith plasma membrane permeability and inhibits bacterial cell wall synthesis in susceptible bacteria. TherapeaticEffect Bacteriostatic. 

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. 

All cephalosporins act by inhibiting bacterial cell wall synthesis and are bactericidal. Also the autolytic enzymes in cell wall may be activated leading to bacterial death. 

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