Antimicrobial Chemotherapy & Resistance – Lecture Review

Vocabulary flashcards covering key terms, concepts, antibiotic classes, mechanisms of action, and resistance discussed in the lecture on antimicrobial chemotherapy and resistance.

Antimicrobial Chemotherapy

Use of drugs to combat infectious agents (bacteria, fungi, parasites, viruses) based on differential toxicity.

Differential Toxicity

Concept that an antimicrobial drug is more toxic to the infecting organism than to the host.

Antibiotic (classical definition)

Substance produced by a microorganism that, in small amounts, inhibits the growth of or kills bacteria.

Alexander Fleming

Discovered the first antibiotic, penicillin, in 1928 from the fungus Penicillium.

Penicillin

β-lactam antibiotic that inhibits bacterial cell-wall synthesis; first mass-produced during WWII.

Bacillus subtilis

Gram-positive rod that produces the antibiotic bacitracin.

Streptomyces griseus

Actinomycete that produces streptomycin.

Ideal Antibiotic

Selective toxicity, bactericidal, narrow spectrum (when possible), low resistance potential, good pharmacokinetics, minimal side effects.

Narrow-Spectrum Antibiotic

Drug effective against a limited range of species, e.g., penicillin against Gram-positives.

Broad-Spectrum Antibiotic

Drug effective against a wide variety of species, e.g., tetracycline against Gram-positive and Gram-negative bacteria.

Minimum Inhibitory Concentration (MIC)

Lowest concentration of an antibiotic that inhibits visible growth of a test organism.

Minimum Bactericidal Concentration (MBC)

Lowest concentration of an antibiotic that kills a test organism.

Bacteriostatic

Drug that inhibits bacterial growth without killing the organism.

Bactericidal

Drug that kills bacteria.

Time-Dependent Killing

Antibacterial activity depends on duration the drug concentration exceeds MIC (e.g., β-lactams).

Concentration-Dependent Killing

Antibacterial activity increases with higher drug concentration (e.g., aminoglycosides, fluoroquinolones).

Prophylaxis (antimicrobials)

Administration of antimicrobial agents to prevent infection.

Peptidoglycan

Polymer of N-acetylglucosamine and N-acetylmuramic acid cross-linked by peptides; main component of bacterial cell walls.

Penicillin-Binding Proteins (PBPs)

Essential enzymes involved in bacterial cell-wall synthesis; targets of β-lactams.

β-Lactam Antibiotics

Penicillins, cephalosporins, cephamycins, carbapenems; inhibit cell-wall synthesis via PBP binding.

Glycopeptide Antibiotics

Vancomycin, teicoplanin; bind D-Ala-D-Ala termini of peptidoglycan precursors, blocking cross-linking.

Polymyxins

Cationic polypeptide antibiotics (e.g., polymyxin B, colistin) that disrupt Gram-negative cell membranes.

Quinolones/Fluoroquinolones

Ciprofloxacin, levofloxacin; inhibit DNA gyrase and topoisomerase IV, blocking DNA replication.

Rifamycins

Rifampicin, rifabutin; inhibit bacterial DNA-dependent RNA polymerase, blocking transcription.

70S Ribosome

Prokaryotic ribosome composed of 50S and 30S subunits; primary target for many protein-synthesis inhibitors.

Macrolides

Erythromycin, clarithromycin, azithromycin; bind 50S subunit to inhibit protein elongation; bacteriostatic.

Lincosamides

Clindamycin; binds 50S subunit; effective against Gram-positives and anaerobes.

Aminoglycosides

Gentamicin, tobramycin; bind 30S subunit causing misreading; bactericidal, concentration-dependent.

Tetracyclines

Bind 30S subunit, blocking tRNA attachment; broad spectrum, bacteriostatic.

Chloramphenicol

Broad-spectrum 50S inhibitor; blocks peptide-bond formation.

Trimethoprim-Sulfamethoxazole (TMP-SMX)

Combination inhibiting sequential steps in folic-acid synthesis; bactericidal synergy.

Antimetabolite

Drug resembling a metabolic substrate that blocks an essential biochemical pathway (e.g., sulfonamides vs PABA).

Viral Replication

Attachment, uncoating, nucleic acid synthesis, protein synthesis, assembly, release—targets for antiviral drugs.

HAART

Highly Active Antiretroviral Therapy; combination of ≥3 anti-HIV drugs to suppress viral load.

Reverse Transcriptase Inhibitors (RTIs)

Antiviral drugs blocking HIV reverse transcriptase, preventing viral DNA synthesis.

Protease Inhibitors (PIs)

Antiviral drugs inhibiting HIV protease, blocking maturation of virions.

Fusion Inhibitors

Drugs preventing fusion of viral envelope with host cell membrane (e.g., enfuvirtide).

Antimicrobial Resistance (AMR)

Ability of microorganisms to withstand antimicrobial treatments that once were effective.

Inherent (Natural) Resistance

Resistance due to intrinsic structural/physiological traits (e.g., outer membrane of Gram-negatives).

Acquired Resistance

Resistance arising from genetic mutation or acquisition of new genes via horizontal/vertical transfer.

Multi-Resistance

Bacterium resistant to multiple antibiotic classes (e.g., Pseudomonas aeruginosa).

Cross-Resistance

Resistance to one antimicrobial confers resistance to other drugs in the same class (e.g., β-lactams).

β-Lactamase

Enzyme that hydrolyses β-lactam ring, rendering β-lactam antibiotics inactive.

Extended-Spectrum β-Lactamase (ESBL)

β-lactamase able to hydrolyse penicillins, cephalosporins, and aztreonam; often plasmid-encoded.

Altered PBP

Resistance mechanism where PBPs mutate (e.g., PBP2a in MRSA) lowering β-lactam affinity.

Vancomycin Resistance (VRSA/VRE)

Change of D-Ala-D-Ala to D-Ala-D-Lac in peptidoglycan precursors, preventing glycopeptide binding.

Efflux Pump

Membrane protein that exports antibiotics from the bacterial cell, lowering intracellular concentration.

Drug Target Modification

Resistance via structural change in antibiotic target, reducing binding (e.g., gyrase mutations vs quinolones).

Enzymatic Drug Inactivation

Resistance through enzymes that chemically modify or destroy antibiotics (e.g., aminoglycoside acetyltransferases).

Antimicrobial Stewardship

Coordinated interventions to improve and measure appropriate antimicrobial use, limiting resistance.

WHO Priority Pathogens (Critical)

A. baumannii, P. aeruginosa, ESBL-producing Enterobacteriaceae—require urgent new antibiotics.

Teixobactin

Novel antibiotic in development targeting lipid II; potential to combat Gram-positive resistance.

Horizontal Gene Transfer

Movement of genetic material between organisms via transformation, transduction, or conjugation.

Vertical Gene Transfer

Transmission of genetic material from parent to offspring during replication.

Proton Motive Force

Energy source powering many bacterial efflux pumps that expel antibiotics.

Selective Permeability (cell membrane)

Property allowing selective entry/exit of substances; disrupted by polymyxins.

Lipopolysaccharide (LPS)

Component of Gram-negative outer membrane targeted by polymyxins.

Porin

Outer-membrane channel protein; mutations can reduce antibiotic uptake, conferring resistance.

Folic Acid Synthesis Pathway

Metabolic route blocked by sulfonamides (PABA analogs) and trimethoprim.

DNA Gyrase

Topoisomerase II enzyme targeted by quinolones in Gram-negative bacteria.

Topoisomerase IV

Enzyme targeted by quinolones in Gram-positive bacteria to decatenate replicated DNA.

Ribosomal 30S Subunit

Target of aminoglycosides and tetracyclines.

Ribosomal 50S Subunit

Target of macrolides, lincosamides, chloramphenicol, streptogramins.

High-Priority Veterinary Use

Mass prophylaxis or growth promotion with antibiotics leading to AMR in zoonotic pathogens.

β-Lactam Ring

Four-membered lactam core essential for activity of β-lactam antibiotics.

Cell-Wall Active Agents

Antibiotics that inhibit peptidoglycan synthesis; generally bactericidal and time-dependent.

Polypeptide Antibiotics

Class including bacitracin and polymyxins; disrupt cell wall or membrane integrity.

Actinomycetes

Soil bacteria (e.g., Streptomyces spp.) producing many natural antibiotics.

Salvarsan

Early antimicrobial (arsenical) used to treat syphilis before modern antibiotics.

Antibiotic Spectrum

Range of bacterial species susceptible to an antibiotic.

Post-Antibiotic Era

Scenario where common infections become untreatable due to widespread resistance.

Antibiotic Stewardship Action

Promote responsible prescribing, infection control, surveillance, and new drug development.

Alternative Therapies (examples)

Phage therapy, antimicrobial peptides, probiotics, CRISPR-based antimicrobials, anti-virulence drugs.