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Cell Wall Synthesis Inhibitors

Antibiotics: cell wall inhibitors FlashCard

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Antibiotics: cell wall inhibitors

Inhibiting the synthesis of the peptidoglycan layer of the bacterial cell wall is a molecular target of many antibacterial drugs including beta-lactam antibiotics (penicillins, cephalosporins, carbapenems & monobactams), and glycopeptides (vancomycin & other newer analogs). The two primary molecular targets for these drugs are transpeptidase enzymes, also referred to as penicillin-binding proteins (PBP), because they bind penicillin, and glycosyltransferase enzymes (GT), which are inhibited by glycopeptides such as vancomycin. There are numerous subtypes of PBPs, and a given bacterial strain can express a variable number of PBPs (e.g. E. coli has been found to express at least 12 subtypes). These PBPs can vary in both their physiological properties, and sensitivity to interaction with antibiotics. Glycosyltransferase enzymes can exist as separate enzymes, or as dimers associated with transpeptidases, depending on the PBP subtype (Sauvage et al, 2008).

Bacterial Cell Wall Synthesis Inhibitors Excreted In Bile

Conditions associated with chronic or intermittent pain includeintestinal infections with Mycobacterium avium-intracellulare andcryptosporidium, which cause cramping and intermittent abdominal pain;hepatosplenomegaly, resulting in abdominal distention and pain; oral andesophageal candidiasis, causing pain while the patient is eating andswallowing; and severe spasticity associated with encephalopathy, whichcauses painful muscle spasms.

cephalosporin and penicillin inhibit cell wall synthesis: ..

Clinical Context: Amoxicillin is an analog of ampicillin with broad-spectrum bactericidal activity against gram-positive and gram-negative microorganisms. It interferes with cell wall mucopeptide synthesis during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Clinical Context: Penicillin inhibits the biosynthesis of cell wall mucopeptide. It is bactericidal against sensitive organisms when adequate concentrations are reached and is most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Penicillin is the drug of choice in treating common orofacial infections caused by aerobic gram-positive cocci and anaerobes. Orofacial infections include cellulitis, periapical abscess, periodontal abscess, acute suppurative pulpitis, oronasal fistula, pericoronitis, osteitis, osteomyelitis, and postsurgical and posttraumatic infections. It is no longer recommended for dental procedure prophylaxis.

Mycobacteria (high lipid content cell wall requires acid ..

However, recent laboratory evidence indicates that triclosan inhibits a specific step in the formation of bacterial lipids involved in the cell wall structure.

Figure 4. Gram-positive Cell Wall Biosynthesis. The bacterial cell wall consists of strands of repeating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) subunits. The NAM subunits have short peptide chains attached to them. The composition of the peptide chain varies between bacteria, but the proximal alanine is usually L-Ala and the distal two are usually D-Ala. Cell wall that also bind penicillin () form bonds between the peptide side chains with the expulsion of a terminal D-Alanine from one of the peptide side chains. The PBP dissociates from the wall once the cross-link has been formed. Separate enzymatic domains with activity form linkages between NAM & NAG residues. Some high molecular mass PBPs (e.g. PBP2) are enzymatic complexes containing both transpeptidase and glycosyltransferase domains (Sauvage et al, 2008). Teichoic acid fibers are found in the cell wall of gram-positive bacteria, and are composed of polymers of either glycerol phosphate or ribitol phosphate. They are involved in the attachment of bacteria to mucosal cells, and can induce septic shock, similar to LPS (endotoxin) released by gram-negative bacteria. Structure of PBP adapted from Mcstrother ().

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Bacterial Cell Wall Synthesis Inhibitors: Aminoglycosides ..

Figure 2. Structural features of the gram-positive bacterial cell wall. Gram-positive bacteria have a thick, multilayered cell wall consisting of peptidoglycan (so named because it contains a mixture of peptides & sugars). Other synonyms for peptidoglycan included murein & mucopeptide. Because peptidoglycan is present in most bacteria, but not in mammalian cells, it is a good target for antibacterial drugs (e.g. cell wall synthesis inhibitors including penicillins, cephalosporins, and vancomycin). These antibiotics interfere with the activity of transpeptidase enzymes (also known as Penicillin Binding Proteins or PBP) in the cell wall that catalyze cross-links between adjacent glycan chains (see Figure 4 for further details). Cell walls also contain fibers of teichoic acid, which facilitate attachment of bacteria to host cell membranes (e.g. mucosal cells), and when released can induce septic shock, similar to that produced by endotoxin (LPS) released by gram-negative bacteria. Beta-lactamases (penicillinases) are a family of enzymes produced by bacteria that can hydrolyze the four atom β-lactone ring of β-lactam antibiotics (many of which are also bacterial in origin), thereby deactivating their antibacterial properties. The bacterial cell membrane can also contain ABC efflux pumps which can contribute to antibiotic resistance, and multi-drug resistance (MDR) against those drugs with an intracellular mechanism of action (e.g. inhibitors of DNA-gyrase or protein synthesis inhibitors). The crystal violet dye adheres to the thick peptidoglycan layer of the cell wall present in gram-positive bacteria, staining them violet or purple when visualized under a light microscope.

Inhibitors of Bacterial Cell Wall (peptidoglycan) ..

The process of Gram staining was developed by a Danish bacteriologist (Hans Christian Gram) who found that bacteria could be differentiated into two large groups based upon different physical properties of their cell walls. Gram-positive bacteria which have a thick peptidoglycan wall retain the crystal violet dye (staining them violet or purple), while all other bacteria (e.g. those having a thin peptidoglycan wall covered by an outer membrane) can be stained pink using a counterstain (safranin or fuchsine) added after the crystal violet dye (see Figure 1) (Murray et al, 2013; ).

carbapenem antibiotic that inhibits bacterial cell wall synthesis

Figure 3. Gram negative bacterial cell wall. Structurally, a gram-negative cell wall consists of two layers external to the cell membrane - a thin layer of peptidoglycan (too thin to absorb a significant amount of methyl violet stain), and an outer membrane (unique to gram-negative bacteria) that typically contains porins that facilitate the diffusion of small (vancomycin (1449 Da) has a mass too large to allow it to permeate through porins to reach its site of action, which makes it ineffective against gram-negative bacteria. Hence the outer membrane provides gram-negative bacteria with an inherent “intrinsic resistance” to some antibiotics, which can be further modified by changes in the expression level of porins, or modification of the pore properties of porins to reduce permeability of antibiotics. The outer membrane of gram-negative bacteria also contains lipopolysaccharide (LPS), or endotoxin, which can be shed by bacteria, causing a powerful immune response by the host.

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