Bacteria cell wall synthesis

The localization of different PBPs and peptidoglycan hydrolases in several bacterial species has been determined using immunofluorescence and, more recently, using GFP-fusions [106, 107,108,109,110]. From these studies, it appears that in coccoid bacteria cell wall synthesis occurs mainly at the septum, while in rod-shaped bacteria different PBPs are localized to sites of cell division and peripheral cell wall synthesis. Furthermore, the localization of the enzymes seems to be dependent on both interactions with other enzymes and with substrate [98]. These visualization techniques have also helped explain the apparent functional redundancy of the PBPs. For example, in S. pneumoniae, different PBPs are speciflcally localized to sites of... 

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. 

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. 

Proanthocyanidins Bacteria Ceii coat poiymers Inhibition of cell-associated proteolysis inhibition of cell wall synthesis [76]... 

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... 

The answer is c. (Hardman, pp 1143-1144.) Bacitracin, cycloserine, cephalothin, and vancomycin inhibit cell-wall synthesis and produce bacteria that are susceptible to environmental conditions. Polymyxins disrupt the structural integrity of the cytoplasmic membranes by acting as cationic detergents. On contact with the drug, the permeability of the membrane changes. Polymyxin is often applied in a mixture with bacitracin and/or neomycin for synergistic effects. 

To be an effective antibacterial agent, a drng mnst inhibit an enzyme that is present in the bacteria bnt not in the host. One well-known example is a transpeptidase involved in cell wall synthesis in some bacteria. Inhibition prevents bacteria from synthesising their cell wall so that proliferation stops. A drng that inhibits this enzyme is the antibiotic, penicillin first nsed in 1941 (see Chapter 17). However, the first dnrg to inhibit bacterial growth was developed from a dye (Box 3.8). 

The reversal of this process could potentially occur with reprotonation from either face of the C=N double bond, and a mixture of aldimines would result, leading to generation of a racemic amino acid. This accounts for the mode of action of PLP-dependent amino acid racemase enzymes. Of course, the enzyme controls removal and supply of protons this is not a random event. One important example of this reaction is alanine racemase, employed by bacteria to convert L-alanine into o-alanine for cell-wall synthesis (see Box 13.12). 

Specific damage to bacteria is particularly practicable when a substance interferes with a metabolic process that occurs in bacterial but not in host cells. Clearly this applies to inhibitors of cell wall synthesis, because human and animal cells lack a cell wall. The points of attack of antibacterial agents are schematically illustrated in a grossly simplified bacterial cell, as depicted in (2). 

Penicillins disrupt cell wall synthesis by inhibiting transpeptidase. When bacteria are in their growth and replication phase, penicillins are bactericidal due to cell wall defects, the bacteria swell and burst. 

Other inhibitors of cell wall synthesis. Bacitracin and vancomycin interfere with the transport of pepti-doglycans through the cytoplasmic membrane and are active only against gram-positive bacteria. Bacitracin is a polypeptide mixture, markedly nephrotoxic and used only topically. Vancomycin is a glycopeptide and the drug of choice for the (oral) treatment of bowel inflammations occurring as a complication of antibiotic therapy (pseudomembranous enterocolitis caused by Clostridium difficile), it is not absorbed. 

Pharmacology Meropenem is a broad-spectrum carbapenem antibiotic. The bactericidal activity of meropenem results from the inhibition of cell-wall synthesis. Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. 

Pharmacoiogy Inhibits cell-wall synthesis in susceptible strains of gram-positive and gram-negative bacteria and in Mycobacterium tubercuiosis. 

Bulgecins were reported for the first time in 1982 [158]. Their structures, such as (94), were established soon afterwards [159, 160] and they were found to interfere with the cell-wall synthesis of gram-negative bacteria due to a unique mechanism inhibiting vital bacterial Soluble Lytic Transglycosylase (SLT) [161]. 

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

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... 

The outer surfaces of bacteria are rich in specialized polysaccharides. These are often synthesized while attached to lipid membrane anchors as indicated in a general way in Eq. 20-20.136/296a One of the specific biosynthetic cycles (Fig. 20-9) that depends upon undeca-prenol phosphate is the formation of the peptidoglycan (murein) layer (Fig. 8-29) of both gram-negative and gram-positive bacterial cell walls. Synthesis begins with attachment of L-alanine to the OH of the lactyl... 

ANTIBIOTICS 0-LACTAMASE INHIBITORS. The antibacterial effectiveness of penicillins, cephalosporins, and other 0-lactam antibiotics depends on selective acylation and consequently, inactivation, of transpeptidases involved in bacterial cell wall synthesis. This acylating ability is a result of the reactivity of the 0-lactam ring (1). Bacteria that are resistant to 0-lactam antibiotics often produce enzymes called 0-lactamases that inactivate the antibiotics by catalyzing the hydrolytic opening of the 0-lactam... 

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