Antibiotics

Cell Wall Targeting Antibiotics

• Transpeptidase is a crucial enzyme that links NAG-NAM units in bacterial cell walls.
• Beta-lactams, such as penicillin, target transpeptidase, disrupting cell membranes and leading to lysis.
• Cephalosporins are beta-lactams resistant to beta-lactamases and have a broad spectrum.
• Glycopeptides, like vancomycin, target the D-ala-D-ala sequence, preventing transpeptidase binding and leading to lysis, but only effective against Gram-positive bacteria.

Ribosome Targeting Antibiotics

• Macrolides target the 50S subunit, are bacteriostatic, and block polypeptide chain translocation.
• Tetracyclines are broad-spectrum, bacteriostatic, and inhibit protein production by blocking tRNA binding to the ribosome.
• Oxazolidones target the 50S subunit, are bacteriostatic, and only effective against Gram-positive bacteria, but expensive, and long-term use can lead to bone marrow suppression.
• Aminoglycosides, such as streptomycin and kanamycin, target the 30S subunit, inhibiting protein biosynthesis and are generally only effective against Gram-negative bacteria.

Nucleic Acid Synthesis Inhibiting Antibiotics

• Quinolones are bactericidal, broad-spectrum, and active against intracellular pathogens, preventing DNA replication by inhibiting DNA gyrase.
• Rifamycins are bactericidal, only effective against Gram-positive bacteria, and inhibit DNA-dependent RNA synthesis by acting on RNA polymerase, thereby inhibiting transcription.

Antibiotic Resistance

• Efflux pumps can resist antibiotics by pumping them out of the cell, contributing to tetracycline resistance.
• β-Lactamases cleave the β-lactam ring, inactivating β-lactam antibiotics, except for carbapenems.
• Transferases alter antibiotic structures, including aminoglycoside-modifying enzymes, often found on MGEs.
• Some bacteria modify the antibiotic target, such as S.aureus, which encodes the mecA gene, producing PBP2 with low affinity for β-lactams.

Antibiotic Development and Resistance Testing

• The MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) help identify resistance and can be determined through broth dilution, disc diffusion, E-test strip, automatic VITEK technology, or genomics.
• Discovering new antibiotics is challenging due to the repetition of searching the same sources and finding the same compounds, making it difficult to identify promising leads.