Antimicrobial Pharmacology, Microbial Pathogenicity, and Host Interactions

Comprehensive review flashcards covering antimicrobial classes, mechanisms of drug action, pharmacological testing, symbiotic relationships, pathogen nomenclature, and molecular mechanisms of bacterial and viral pathogenesis.

Antimicrobials

Chemical compounds that kill microorganisms or stop their growth, encompassing antibiotics, antifungals, antiprotozoals, and antivirals.

Natural Antimicrobials

Antimicrobial compounds derived directly from microbes or plants that naturally produce these substances to inhibit or kill competitors (e.g., penicillin, actinomycin, streptomycin, and neomycin).

Semisynthetic Antimicrobials

Chemical derivatives of naturally occurring antimicrobials modified in the laboratory to improve therapeutic properties, broaden spectrum, or decrease toxicity (e.g., ampicillin, amoxicillin).

Synthetic Antimicrobials

Antimicrobial therapeutics developed entirely from chemical compounds not found in nature, originally pioneered by Gerhard Domagk with sulfanilamide.

Broad-spectrum Antimicrobials

Antimicrobial drugs active against a wide variety of microbial targets (such as both Gram-positive and Gram-negative bacteria), commonly prescribed for polymicrobial infections or empirical therapy prior to pathogen identification.

Narrow-spectrum Antimicrobials

Antimicrobial agents that target only specific subsets of microorganisms (e.g., only Gram-positive or only Gram-negative bacteria), chosen when the causative pathogen is identified to minimize damage to normal flora.

Superinfection

A secondary infection that develops when broad-spectrum antimicrobial therapy eliminates the protective normal microbiota, allowing opportunistic or drug-resistant organisms (e.g., Clostridium difficile or Candida spp.) to proliferate.

Microbicidal

An antimicrobial action that causes irreversible cell death of targeted pathogens, which can sometimes trigger massive endotoxin (LPS) release and septic shock during Gram-negative infections.

Microbiostatic

An antimicrobial property that reversibly arrests the growth and replication of microbes, relying on an intact host immune system to eliminate the pathogen.

Minimal Inhibitory Concentration (MIC)

The lowest concentration of an antimicrobial drug that visibly inhibits the growth of a bacterial strain in broth dilution or gradient strip assays.

Minimal Bactericidal Concentration (MBC)

The lowest drug concentration that kills $> 99.9\%$ of the initial bacterial inoculum, determined by plating samples from tubes with no visible growth from a broth dilution assay.

Kirby-Bauer Disk Diffusion Test

A standardized agar diffusion assay using antibiotic-impregnated paper disks placed on a bacterial lawn to determine susceptibility by measuring zones of inhibition.

Etest

A plastic strip antimicrobial susceptibility assay combining dilution and diffusion principles, featuring an antibiotic gradient to produce an elliptical zone of inhibition that intersects at the MIC.

Beta-lactams

A class of cell wall inhibitors containing a characteristic four-membered beta-lactam ring that structurally mimics peptidoglycan subunits, binding to and inhibiting penicillin-binding proteins (PBPs).

Penicillin-binding Proteins (PBPs)

Bacterial transpeptidase enzymes responsible for cross-linking peptide chains during peptidoglycan cell wall biosynthesis, which serve as the primary targets of beta-lactam antibiotics.

Vancomycin

A large glycopeptide antibiotic that binds directly to the terminal D-Ala-D-Ala of cell wall precursors, preventing peptidoglycan transglycosylation and transpeptidation in Gram-positive bacteria.

Bacitracin

A narrow-spectrum peptide antibiotic that blocks the lipid carrier bactoprenol from transporting peptidoglycan precursors across the cytoplasmic membrane; restricted largely to topical applications due to nephrotoxicity.

Polymyxins

Lipopeptide antibiotics, including polymyxin B and colistin (polymyxin E), that target lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, disrupting membrane structure.

Daptomycin

A natural cyclic lipopeptide antibiotic that inserts selectively into the cytoplasmic membrane of Gram-positive bacteria, causing rapid membrane depolarization and cell death.

Aminoglycosides

Bactericidal antibiotics (e.g., streptomycin, gentamicin) that bind the 30S ribosomal subunit, causing mistranslation and proofreading errors that result in faulty proteins inserting into and disrupting the cytoplasmic membrane.

Tetracyclines

Broad-spectrum bacteriostatic antibiotics that bind reversibly to the 30S ribosomal subunit, physically sterically hindering tRNA from binding to the ribosomal A-site.

Chloramphenicol

A broad-spectrum bacteriostatic antibiotic that binds to the 50S ribosomal subunit and halts peptide bond formation; restricted clinically due to toxic suppression of mitochondrial protein synthesis in bone marrow stem cells.

Oxazolidinones

Synthetic broad-spectrum antibiotics (e.g., linezolid) that bind the 50S ribosomal subunit P-site, preventing the binding of fMet-tRNA and blocking formation of the translation initiation complex.

Fluoroquinolones

Synthetic broad-spectrum bactericidal antibiotics (such as ciprofloxacin and levofloxacin) that inhibit bacterial DNA gyrase and topoisomerase IV, preventing DNA replication.

Metronidazole

A nitroimidazole prodrug that is partially reduced in anaerobic bacteria and protozoa to generate toxic free radicals that induce lethal DNA strand breakage.

Rifamycins

Semisynthetic bactericidal antibiotics (e.g., rifampin) that bind specifically to the beta subunit of bacterial RNA polymerase, blocking RNA transcript elongation.

Antimetabolites (Folic Acid Inhibitors)

Synthetic inhibitors like sulfonamides and trimethoprim that competitively block consecutive enzymes in tetrahydrofolic acid biosynthesis, acting synergistically to kill bacteria.

Bedaquiline

A synthetic diarylquinoline antibiotic that specifically inhibits mycobacterial ATP synthase, utilized as a reserve medication for multidrug-resistant tuberculosis.

Ergosterol

The predominant sterol in fungal cell membranes, analogous to cholesterol in mammalian cells, serving as the selective target for azoles, allylamines, and polyenes.

Acyclovir

A synthetic guanosine nucleoside analog selectively activated by viral thymidine kinase that acts as an obligate chain terminator during viral DNA polymerase replication.

Symbiosis

Any type of close, long-term biological interaction between two different organisms, which may be beneficial, neutral, or harmful to either party.

Mutualism

A symbiotic relationship in which both interacting populations benefit from the association (e.g., gut microbiota aiding digestion and immune development while receiving nutrients).

Commensalism

A symbiotic relationship wherein one organism benefits while the other is unaffected (neither helped nor harmed), such as Malassezia fungi utilizing sebum on human skin.

Amensalism

A symbiotic interaction in which one population is harmed or inhibited while the other organism remains completely unaffected.

Parasitism

A symbiotic relationship in which one organism benefits at the direct expense of the host organism, which is harmed by the association.

Resident Microbiota

Microorganisms that permanently and stably inhabit specific anatomical sites in and on a host organism under healthy conditions.

Transient Microbiota

Microorganisms that are only temporarily found on or inside a host organism without establishing persistent colonization.

Signs

Objective and measurable indications of an infection or disease (e.g., body temperature, heart rate, white blood cell count) observed or measured by an examiner.

Symptoms

Subjective manifestations of disease experienced and felt directly by the patient (e.g., nausea, pain, malaise) that cannot be directly measured clinically.

Iatrogenic Disease

A condition or infection acquired directly as an unintended result of medical intervention, surgery, catheterization, or drug treatment.

Nosocomial Disease

An infectious disease acquired specifically within a clinical or hospital setting after patient admission.

Zoonosis

An infectious disease transmitted under natural conditions from vertebrate animals to humans.

Median Infectious Dose ($ID_{50}$)

The number of pathogenic cells, virions, or cysts required to establish an active infection in 50% of inoculated experimental subjects.

Median Lethal Dose ($LD_{50}$)

The number of pathogenic organisms, virions, or concentration of toxin required to kill 50% of an infected experimental group.

Primary Pathogen

A disease-causing microorganism that can establish infection and cause pathology in an individual regardless of the status of their immune defenses or resident microbiota.

Opportunistic Pathogen

A microbe that typically only causes disease when host defenses are weakened (e.g., immunosuppression, epithelial breach, or normal flora disruption).

Incubation Period

The initial stage of an acute infection following exposure and entry of the pathogen, during which microbial replication occurs without observable signs or symptoms.

Koch's Postulates

A historical four-step protocol published in 1884 to establish whether a specific cultivable microorganism is the causative agent of a specific disease.

Falkow's Molecular Koch's Postulates

A set of molecular criteria formulated in 1988 establishing that a suspected virulence gene must be present in pathogenic strains, its inactivation must reduce virulence, and its restoration must recover virulence.

Fredricks and Relman's Postulates

Sequence-based molecular criteria established in 1996 for correlating uncultivable infectious agents with disease based on nucleic acid sequence presence, copy number, and resolution.

Adhesins

Macromolecular surface proteins or glycoproteins (e.g., fimbriae, pili, capsular components) used by pathogens to adhere specifically to complementary receptors on host cells.

Exoenzymes

Extracellular virulence enzymes secreted by pathogens to degrade extracellular matrix components, penetrate tissue barriers, and acquire nutrients without directly intoxicating cells.

Hyaluronidase

A bacterial glycohydrolase exoenzyme that cleaves hyaluronan (hyaluronic acid) in the extracellular matrix, facilitating the spread of bacteria through connective tissues.

Collagenase

A bacterial protease exoenzyme (such as in Clostridium perfringens) that hydrolyzes collagen fibrils in dense connective tissue, promoting invasive tissue spread.

Coagulase

An enzyme produced by Staphylococcus aureus that reacts with plasma factors to convert fibrinogen into fibrin, creating protective clots that insulate bacteria from phagocytosis.

Endotoxin

The toxic lipid A moiety of lipopolysaccharide (LPS) anchored in the outer membrane of Gram-negative bacteria, released during cell division or lysis to trigger inflammatory cascades and septic shock.

A-B Exotoxins

Two-component protein exotoxins consisting of a catalytic 'A' subunit that mediates enzymatic toxicity and a binding 'B' subunit that mediates cellular receptor specificity and entry.

Cholera Toxin

An enterotoxic A-B exotoxin produced by Vibrio cholerae that locks Gs alpha proteins in an active state via ADP-ribosylation, hyperstimulating adenylate cyclase and opening CFTR chloride channels to produce profuse watery diarrhea.

Superantigens

Bacterial exotoxins (e.g., TSST-1) that bridge MHC class II molecules and T-cell receptors non-specifically outside the peptide groove, triggering massive polyclonal T-cell activation and cytokine storm.

Antigenic Drift

The accumulation of point mutations within viral genes encoding surface antigens (such as influenza hemagglutinin and neuraminidase), resulting in minor antigenic changes that evade antibody recognition.