Mechanisms of Antimicrobial Action and Resistance

Comprehensive vocabulary flashcards covering the mechanisms of action, molecular targets, clinical uses, and resistance mechanisms of major antibacterial and antimicrobial drug classes.

Transpeptidase

Also known as penicillin binding protein (PBP); an essential bacterial enzyme that cross-links NAM subunits during peptidoglycan cell wall synthesis.

Beta-lactams

A major class of cell wall synthesis inhibitors characterized by a beta-lactam ring; they act as alanine analogues that bind PBPs to block transpeptidation, weakening the cell wall until the bacterium lyses from osmotic pressure.

Beta-lactamase (Penicillinase)

A bacterial resistance enzyme that hydrolyzes and breaks a specific bond within the beta-lactam ring, converting active penicillin into inactive penicillin.

Beta-lactamase Inhibitors

Molecules such as clavulanic acid and tazobactam combined with penicillins (e.g., piperacillin-tazobactam, amoxicillin-clavulanic acid, ceftolozane-tazobactam) to inhibit the beta-lactamase enzyme and prevent antibiotic destruction.

Semisynthetic Beta-lactams

Chemically altered derivatives of natural beta-lactams designed to be more stable in acidic environments, more readily absorbed, less susceptible to deactivation, and effective against a broader spectrum of bacteria.

Bacitracin

An antibacterial agent that inhibits cell wall synthesis by blocking the transport of NAG and NAM subunits across the cytoplasmic membrane from the cytoplasm.

Isoniazid and Ethambutol

Antimicrobial agents that inhibit cell wall synthesis by specifically disrupting the synthesis and formation of mycolic acid in mycobacterial species.

Vancomycin

A glycopeptide antibiotic that binds to the D-ala-D-ala terminal moiety of peptidoglycan precursors, interfering with bridges that link NAM subunits in Gram-positive bacteria; must be given orally (po) for Clostridium difficile infections.

Vancomycin Resistance Mechanism

A genetic target modification observed primarily in Enterococcus and S. aureus where bacteria alter the D-ala-D-ala binding target by substituting D-lac for the terminal D-ala, preventing vancomycin from binding.

Fosfomycin

A cell wall synthesis inhibitor that acts intracellularly by preventing the initial synthesis of peptidoglycan cell wall precursors in the bacterial cytoplasm.

Aminoglycosides

Bactericidal antibiotics with a cyclohexane ring and amino sugars (e.g., streptomycin) that bind the 30S ribosomal subunit, causing a conformational change that induces mRNA misreading; they do not work in anaerobic environments and require therapeutic drug monitoring.

Tetracyclines

Broad-spectrum, bacteriostatic protein synthesis inhibitors with a four-ring structure that bind the 30S ribosomal subunit to physically block the docking site of aminoacyl-tRNA; adverse effects include tooth discoloration, photosensitivity, skeletal growth depression, and esophageal ulceration.

Macrolides

Broad-spectrum, bacteriostatic antimicrobials containing 12- to 22-carbon lactone rings linked to sugars (e.g., erythromycin) that bind to the 50S ribosomal subunit and block proper mRNA movement through the ribosome; frequently used as an alternative for penicillin-allergic patients.

Sulfonamides

Antimetabolic drugs that are structural analogues of para-aminobenzoic acid (PABA); they competitively inhibit bacterial folic acid synthesis, thereby halting the downstream production of purine and pyrimidine nucleotides required for DNA and RNA synthesis.

Atovaquone

An antimetabolic agent that disrupts pathogen energy metabolism by interfering with the electron transport chain in protozoa and fungi.

DNA Gyrase

An essential bacterial topoisomerase that catalyzes the negative supercoiling of double-stranded, closed-circular DNA during replication; targeted by quinolones and fluoroquinolones.

Fluoroquinolones

Broad-spectrum, bactericidal synthetic agents possessing a fluorinated 4-quinolone ring (e.g., ciprofloxacin) that disrupt DNA replication by inhibiting bacterial DNA gyrase and topoisomerase IV.

Rifamycins (Rifampin)

Semisynthetic antimicrobial agents that inhibit bacterial transcription by binding directly to the $\beta$-subunit of RNA polymerase; primarily indicated in the treatment of tuberculosis.

Metronidazole (Flagyl)

An antimicrobial with little to no activity against aerobes that undergoes reduction in anaerobic environments to generate short-lived toxic intermediates and free radicals (such as nitroradical anions), damaging DNA and inhibiting nucleic acid synthesis.

Multiple-Drug-Resistant (MDR) Pathogens

Microbial pathogens that demonstrate acquired resistance to at least three distinct classes of antimicrobial agents, commonly emerging in clinical environments such as hospitals and nursing homes.

Cross Resistance

A resistance profile where a single physiological mechanism or genetic determinant confers resistance to multiple antimicrobial agents sharing similar chemical structures.

Synergism

An antimicrobial interaction in which the combined therapeutic activity of two drugs is significantly greater than the effect of either drug alone (e.g., amoxicillin-clavulanic acid combined with aztreonam).

Antagonism

A drug interaction occurring when the administration of two antimicrobial agents results in one drug interfering with or reducing the clinical effectiveness of the other.

TMP-SMX (Trimethoprim-Sulfamethoxazole)

A synergistic antimicrobial combination that inhibits sequential steps of bacterial folate metabolism; resistance arises via drug-resistant variants of DHFR / THPS or metabolic bypass.

R Plasmids

Extrachromosomal resistance plasmids acquired by bacteria through horizontal gene transfer (transformation, transduction, or conjugation) that carry genes conferring resistance to one or more antimicrobial agents.