Protein synthesis bacterial

As in any cell, bacteria must be able to replicate their genetic material to reproduce and function normally. An inability to produce normal DNA and RNA will prohibit the bacteria from mediating continued growth 

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It has been known for some time that tetracyclines are accumulated by bacteria and prevent bacterial protein synthesis (Fig. 4). Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect (85). Inhibition of protein synthesis results primarily from dismption of codon-anticodon interaction between tRNA and mRNA so that binding of aminoacyl-tRNA to the ribosomal acceptor (A) site is prevented (85). The precise mechanism is not understood. However, inhibition is likely to result from interaction of the tetracyclines with the 30S ribosomal subunit because these antibiotics are known to bind strongly to a single site on the 30S subunit (85). 

Oxazolidinones are a new class of synthetic antimicrobial agents, which have activity against many important pathogens, including methicillin-resistant Staphylococcus aureus and others. Oxazolidinones (e.g. linezolid or eperezolid) inhibit bacterial protein synthesis by inhibiting the formation of the 70S initiation complex by binding to the 50S ribosomal subunit close to the interface with the 3OS subunit. 

Spectinomycin (Trobicin) is chemically related to but different from the aminoglycosides (see Chap. 10). This drug exerts its action by interfering with bacterial protein synthesis. Spectinomycin is used for the treatment of gonorrhea... 

Brandi, L., Lazzaroni, A., Cavalletti, L., Abbondi, M., Corti, E., Ciciliato, I., Gastaldo, L., Marazzi, A., Feroggio, M., Maio, A., Colombo, L., Donadio, S., Marinelli, F., Losi, D., Gualerzi, C. O., and Selva, E. (2006c). Novel tetrapeptide inhibitors of bacterial protein synthesis produced by a streptomyces. Biochemistry 43, 3700—3710. 

The oxazolidinones have a novel mechanism of action that involves the inhibition of bacterial protein synthesis at the very early stage, prior to chain initiation [55-58]. They are effective against a broad range of Gram-... 

Bacterial protein synthesis is directly correlated to bacterial activity and can be determined by incorporation of 3H or 14C leucine, as this amino acid is incorporated into proteins only. The method for leucine incorporation (Baath 1994) is the same as for thymidine incorporation in case of DNA synthesis and the incorporation of both precursors can be carried out in a single assay if different radiolabels are used. 

Tetracyclines are a group of antibiotics derived from bacteria. Chlortet-racycline was isolated from Streptomyces aureofaciens and oxytetracycline from Streptomyces rimosus. Tetracychnes act by binding to receptors on the bacterial ribosome and inhibit bacterial protein synthesis. 

The ansamycins (rifamycin B and rifamycin SV) are produced by certain strains of Nocardia mediterranei and act by inhibition of messenger RNA (m-RNA) synthesis, and consequently of bacterial protein synthesis. Structurally, they present a characteristic ansa structure, made of a ring containing a naphthohydroquinone system spanned by an aliphatic chain. The two ansamycins differ in the type of substituent on the... 

Aminoglycoside a structurally complex antibacterial that works as bacterial protein synthesis inhibitor. 

Tetracycline one of a class of antibacterials based on a tetracyclic skeleton and that act as a bacterial protein synthesis inhibitors. 

Aminomethyl- cyclines Amino- methyl- cycline MK-2764 (PTK-0796 BAY 73-7388) (153) Antibacterial (broad spectrum antibiotic against MRS A, MDR Streptococcus pneumoniae and vancomycin-resistant enterococci) Inhibits bacterial protein synthesis Phase III (treatment of hospital infections in both oral and i.v. injectable formulations) Paratek/Novartis 810... 

Erythromycin inhibits bacterial protein synthesis by reversibly binding with their 50 S ribosomal subunit, thus blocking the formation of new peptide bonds. Erythromycin is classified as a bacteriostatic antibiotic. 

In many ways, mitochondria resemble bacteria for example, the mitochondrial ribosomal RNA genes of all eukaryotes have been traced back to the eubacteria [10]. This can explain why some antibacterial compounds with the target of inhibiting bacterial protein synthesis also inhibit mitochondrial protein synthesis [6, 11, 12], resulting in hematotoxicity. Tetracycline, chloramphemcol and some oxazolidinone antibiotics have been shown to induce hematotoxicity by inhibiting mitochondrial protein synthesis [13]. 

Clindamycin is a chlorine-substituted derivative of lincomycin. However it is more potent and is better absorbed from the gastrointestinal tract and has therefore replaced lincomycin in most situations. Clindamycin is in principle a bacteriostatic agent. Its indications are mainly limited to mixed anaerobic infections. As mentioned above it has a similar mechanism of action as erythromycin. It selectively inhibits bacterial protein synthesis by binding to the same 50s ribosomal subunits. Erythromycin and clindamycin can interfere with each other by competing for this receptor. Also cross-resistance with erythromycin frequently occurs. Resistance is rather chromosomal rather than plasmid mediated and is especially found in cocci and Clostridium difficile. 

Chloramphenicol is able to inhibit the peptidyl transferase reaction and so bacterial protein synthesis by binding reversibly to the 50s ribosomal subunit. Resistance can occur due to the plasmid-mediated enzyme chloramphenicol acetyltransferase which inactivates the drug by acetylation. Such resistance is often a part of plasmid-mediated multidrug resistance. Resistance can also occur by an altered bacterial permeability. However in most instances resistance to chloramphenicol only develops slowly and remains partial. 

Fusidic acid is a product of, among others, the fungus Fusidium coccineum. It has a steroidal structure and has mainly bacteriostatic activity. Its mechanism of action is based on inhibition of bacterial protein synthesis. Its indications are limited to the treatment of severe staphylococcal infections, usually in combination with another antistaphylococcal agent to prevent the emergence of resistance. 

These antibiotics are considered as a choice of last resort where every other antibiotic therapy has failed. The first and only commercially available oxazolidinone antibiotic is linezolid which was introduced in 2002. Its mechanism of action is inhibition of bacterial protein synthesis. It is available for intravenous administration and also has the advantage of having excellent oral bioavailability. Linezolid is used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRS A). 

Mupirocin is not related to any of the sys-temically used antibiotics. It is an inhibitor of bacterial protein synthesis and is especially active against gram-positive aerobic bacteria, e.g. methicillin-resistant S. aureus and group A beta-hemolytic streptococci. Absorption through the skin is minimal. Intranasal application may be associated with irritation of mucous membranes. 

Typical classes and examples within these categories as they apply to what is currently most prescribed on the U.S. market are summarized in Table 1.8. The targets in groups 1 and 4 are unique in bacteria and absent in humans and other animals, whereas groups 2, 3, and 5 have human counterparts that are structurally different between prokaryotes and eukaryotes. These differences in targets make the use of antibiotics selective for bacteria with little or no effect on eukaryotic cells from a therapeutic perspective. However, that does not mean that antimicrobial compounds are completely inert to eukaryotes. The mechanisms that block bacterial protein synthesis, block DNA replication, and those that disrupt membrane integrity affect membrane pores. 

Mechanism of Action A dichloroacetic acid derivative that inhibits bacterial protein synthesis by binding to bacterial ribosomal receptor sites. Therapeutic Effect Bacteriostatic (maybe bactericidal in high concentrations). 

Mechanism of Action A tetracycline antibacterial that inhibits bacterial protein synthesis by binding to ribosomal receptor sites also inhibits ADH-induced water reabsorption. Therapeutic Effect Bacteriostatic also produces water diuresis. Pharmacokinetics Food and dairy products interfere with absorption. Protein binding 41 %-91%. Metabolized in liver. Excreted in urine. Removed by hemodialysis. Half-life 10-15 hr. 

Mechanism of Action A macrolide that binds to ribosomal receptor sites of susceptible organisms, inhibiting bacterial protein synthesis. Therapeutic Effect Bactericidal or bacteriostatic, depending on drug dosage. 

Mecfianism of Action A macrolide that reversiblybindstobacterial ribosomes, inhibiting bacterial protein synthesis. Therapeutic Effect Bacteriostatic. Pharmacokinetics Variably absorbed from the GI tract (depending on dosage form used). Protein binding 70%-90%. Widely distributed. Metabolized in the liver. Primarily eliminated in feces by bile. Not removed by hemodialysis. Half-life 1.4-2 hr (increased in impaired renal function). 

Mechanism of Action An aminoglycoside antibacterial that binds to bacterial microorganisms. Therapeutic Effect Interferes with bacterial protein synthesis. Pharmacokinetics Poorly absorbed from the GI tract following PO administration. Protein binding Low. Primarily eliminated unchanged in the feces minimal excretion in urine. Removed by hemodialysis. Half-life 3 hr. 

Mechanism of Action An antibacterial agent that acts directly on amebas and against normal and pathogenicorganisms in the G1 tract, Interferes with bacterial protein synthesis by binding to 305 ribosomal subunits TherapeuticEffect Producesamebicidal effects. 

Mechanism of Action An aminoglycoside that binds directly to the 303 ribosomal subunits causing a faulty peptide sequence to form in the protein chain. Therapeutic Effect Inhibits bacterial protein synthesis. 

Streptomycin and other aminoglycosides inhibit bacterial protein synthesis by binding... 

Figure 9.3 Targets for antibacterial drugs. The various classes of antibacterial drugs exert their effects at one of the four fundamental structural components of bacteria. Each of these components is vulnerable to drug attack. Penicillin, for example, attacks at the level of the cell wall chloramphenicol, however, works at the level of bacterial protein synthesis.

Tetracycline Prevents bacterial protein synthesis by binding to the 30S ribosomal subunit Bacteriostatic activity against susceptible bacteria Infections caused by mycoplasma, chlamydiae, rickettsiae, some spirochetes malaria H pylori acne Oral mixed clearance (half-life 8 h) dosed every 6 h divalent cations impair oral absorption Toxicity Gastrointestinal upset, hepatotoxicity, photosensitivity, deposition in bone and teeth... 

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