Antibiotics

Introduction of Antibiotics their mechanisms of action and cellular targets.

• Antibiotics are antimicrobials that can kill or inhibit growth of susceptible organisms.


• Antibiotics are targeted antimicrobials that usually affect a metabolic pathway.


• Beta lactam-A beta-lactam ring or penam: is a lactam consisting of a heteroatomic ring structure containing three carbons and one nitrogen atom.


• Beta Lactams Antibiotics bind and inhibit enzymes involved in cell wall synthesis.  Little effect on non replicating bacteria.  Lethal to dividing bacteria.


• Penicillin: is an antibiotic used to treat bacterial infections (usually Gram-positive).  Originally derived from the blue-green mold Penicillium.


• Penicillin binds irreversibly to transpeptidase and prevents it from cross linking the peptidoglycan units of the cells wall.


• Cephalosporin: beta-lactam family of antibiotics, bactericidal, prevents cell wall synthesis. 


• Tetracycline: interfere with protein synthesis by binding to ribosomes.


• Glycopeptides are molecules that work by interfering with the synthesis of bacterial cell walls.


• Polymyxin: antibiotic damages the cytoplasmic membrane of bacteria.  Polymyxin is produced by the bacteria Bacillus polymyxa.  Increase the permeability of bacterial cell membranes causing a loss of equilibrium.


• Aminoglycosides:  is a collections of antibiotics that target the cells ribosome and cause error prone reading of the mRNA inhibiting protein synthesis.  Aminoglycosides include: amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, tobramycin and apramycin. 


• Rifampin is derived from rifamycin and interferes with RNA synthesis by binding to RNA polymerase.


• Antifungal drugs inhibit the growth of fungi.  Typically toxic to humans because both organisms are eukaryotic.  Examples include: imidazole, clotrimazole, ketoconazole, miconazole and others.  They extract membrane sterols or prevent their synthesis.


• Antibiotics can be synthetically produced.  Alternatively organisms producing antibiotics can be grown in fermentation flasks and the products separated.


• Antibiotic resistance to beta lactams is a result of an enzyme called beta lactamase which break the beta lactam ring.  The gene for the enzyme can be transferred between bacteria resulting in resistance.

Antibiotic Targets

• Cell Wall which provides the bacteria a outer protection and mediates the amount of liquid that can enter and leave the cell.


• Cell Membrane: is a lipid bilayer and functions as a permeability barrier.


• Cellular Proteins:  these targets can include ribosomes and other proteins vital for cell metabolism and reproduction.


• Cellular Nucleic Acids: interfere with DNA production.


• Many antibiotics, fungicides, antimalarials and antivirals act on the DNA or RNA of a cell.


• Gene function may be suppressed by inhibiting nucleic acid or protein biosynthesis.


• Enzyme Inhibition: irreversible or reversible binding or competitive inhibition of cell enzymes.

Antimetabolites

• Chemotherapy exploits the biochemical differences between host and pathogen.


• Metabolites are substances used or produced by biochemical reactions.


• Antimetabolite is a drug or chemical that has chemical similarity (is a mimic) to a natural metabolite.


• Sulfa Drugs and it analogs were the first ant metabolite successfully used against microbes.


• Folic Acid analogs block the final conversion of PABA to folic acid which results in nucleotide and protein synthesis inhibition in bacteria.


• Gram-Positive bacteria have multiply layers of  peptidoglycan stacked to form the cell wall. The peptidoglycan portion of the cell wall consists of repeating units of N-acetylglucosamine linked b-1,4 to N-acetylmuramic acid (NAG-NAM).