Antibiotics | Cell Wall Inhibitors | Microbiology | Basic Science Series

Antibiotics | Cell Wall Inhibitors | Microbiology | Basic Science Series
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1. Discovery of Penicillin:
• Alexander Fleming discovered that Penicillium
• This led to the development of penicillin, the first antibiotic.
• Penicillin had strong antibacterial effects and was safe to use.
2. Protosil and Sulfanilamide:
• In 1935, a significant advance in treating bacterial infections occurred.
• Before this, antiseptics were only used on the skin
• That year, the dye protosil was found to protect mice
• Protosil breaks down in the body to release sulfanilamide, the first effective "sulfa" drug.
3. Development of New Antibiotics and Resistance:
• Recently, new antibiotics have been developed more slowly.
• New types like ketolides and glycylcyclines have been introduced.
• However, bacteria have become resistant to many drugs.
• This means antibiotics are not a perfect solution for all infections.
4. Bacterial Cell Wall Structure:
• The main component of most bacterial cell walls is the peptidoglycan layer.
• It is made up of chains of disaccharide residues of Nacetylglucosamine and Nacetylmuramic acid.
• These chains are crosslinked by peptide bridges, forming a rigid mesh around the bacteria.
• Enzymes such as transpeptidases, transglycosylases, and carboxypeptidases facilitate the assembly of these chains and crosslinks.
• These enzymes are serine proteases also known as penicillinbinding proteins (PBPs).
5. βlactam Antibiotics:
• PBPs are the targets of βlactam antibiotics.
• When these antibiotics bind to PBPs, they inhibit the formation of peptidoglycan chains.
• This activates autolysins that degrade the cell wall, leading to bacterial death.
• Thus, βlactam antibiotics are typically bactericidal.
6. Disruption of Bacterial Cell Walls:
• Various antibiotics disrupt bacterial cell walls.
• Penicillins, cephalosporins, cephamycins, carbapenems, and monobactams are all βlactam antibiotics.
• These antibiotics bind to penicillinbinding proteins (PBPs) and enzymes responsible for peptidoglycan synthesis, inhibiting cell wall construction.
7. βlactamase Inhibitors:
• βlactamase inhibitors function by binding to βlactamases.
• This prevents these enzymes from inactivating βlactam antibiotics, enhancing the efficacy of the antibiotics.
8. Other Antibiotics and Their Mechanisms:
• Vancomycin disrupts cell wall integrity by inhibiting the crosslinkage of peptidoglycan layers.
• Daptomycin causes depolarization of the bacterial cytoplasmic membrane, leading to disruption of ionic concentration gradients and ultimately cell death.
• Bacitracin interferes with the bacterial cytoplasmic membrane and the movement of peptidoglycan precursors.
• Polymyxins target and inhibit bacterial membranes directly.
9. Inhibition of Mycolic Acid and Arabinogalactan Synthesis:
• Antibiotics like isoniazid and ethionamide inhibit the synthesis of mycolic acid, a key component of the cell wall in mycobacteria.
• Ethambutol obstructs arabinogalactan synthesis, another essential component of the mycobacterial cell wall.
• Cycloserine prevents the crosslinkage of peptidoglycan layers, further compromising the structural integrity of bacterial cell walls.
• These various mechanisms collectively contribute to the effectiveness of antibiotics in combating bacterial infections.
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