chapter 14 micro biology

Chemotherapy

The broad term for any use of chemicals or drugs to treat disease, including both cancer treatments and antimicrobial drugs.

Ancient antimicrobial use

Evidence includes tetracycline residue in ancient Nubian skeletal remains (from fermented beer using Streptomyces), and traditional use of medicinal plants by Chinese and Indian herbalists (e.g., Tu Youyou's use of Artemisia, based on a 4th-century text, to develop a malaria cure).

Paul Ehrlich

German physician/scientist who systematically screened arsenic compounds to find a "magic bullet" against microbes without harming the patient; his assistant Sahachiro Hata found Compound 606 (Salvarsan), effective against syphilis (1909).

Compound 606 (Salvarsan)

The first modern antimicrobial "magic bullet," discovered by Hata under Ehrlich, targeting Treponema pallidum (syphilis).

Prontosil / sulfanilamide

A synthetic dye discovered by Klarer, Mietzsch, and Domagk to treat streptococcal/staphylococcal infections; its active breakdown product, sulfanilamide, was the first synthetic antimicrobial, founding the sulfa drug family. Domagk won the 1939 Nobel Prize.

Alexander Fleming

Scientist who in 1928 accidentally discovered that Penicillium notatum mold inhibited staphylococcal growth, leading to the discovery of penicillin, the first natural antibiotic.

Howard Florey and Ernst Chain

Oxford researchers who purified penicillin and demonstrated its efficacy in animal/human trials (1940); shared the 1945 Nobel Prize with Fleming.

Dorothy Hodgkin

Determined the structure of penicillin (1946) using X-ray crystallography, enabling development of semisynthetic penicillins; won the 1964 Nobel Prize in Chemistry.

Selman Waksman

Soil microbiologist who led the discovery of several antimicrobials (actinomycin, streptomycin, neomycin) from Streptomyces and other Actinobacteria; won the 1952 Nobel Prize (with collaborators Albert Schatz and Elizabeth Bugie contributing significantly but receiving less credit).

Natural antimicrobial

A drug produced naturally by a living organism (e.g., penicillin from Penicillium, streptomycin from Streptomyces).

Semisynthetic antimicrobial

A chemically modified derivative of a natural antibiotic, designed to improve spectrum, stability, or reduce toxicity (e.g., ampicillin, methicillin).

Synthetic antimicrobial

A drug developed entirely from chemicals not found in nature (e.g., sulfanilamide, fluoroquinolones).

Bacteriostatic

A drug activity that reversibly inhibits bacterial growth; growth resumes once the drug is removed.

Bactericidal

A drug activity that kills the target bacteria.

Narrow-spectrum antimicrobial

A drug that targets only a specific subset of bacteria (e.g., only gram-positive or only gram-negative), minimizing damage to normal microbiota.

Broad-spectrum antimicrobial

A drug effective against a wide variety of bacteria (gram-positive and gram-negative); used for empiric therapy, polymicrobic infections, or prophylaxis.

Superinfection

A secondary infection that develops when a broad-spectrum antimicrobial kills protective normal microbiota, allowing a resistant pathogen to proliferate (e.g., Candida yeast infections, C. difficile colitis).

Dosage

The amount of medication given over a specific time interval, balanced to achieve therapeutic levels while minimizing toxicity; influenced by patient mass, age, and liver/kidney function.

Half-life (drug)

The time required for 50% of a drug to be eliminated from plasma; influences dosing frequency.

Route of administration

The method of introducing a drug into the body (e.g., oral, parenteral/IV or IM, topical); affects absorption and plasma drug concentration.

Synergistic drug interaction

A combination of two drugs producing a greater effect together than either alone (e.g., trimethoprim + sulfamethoxazole, individually bacteriostatic, together bactericidal).

Antagonistic drug interaction

A combination of drugs producing a harmful or reduced effect (e.g., antacids reducing absorption of certain antibacterials).

Selective toxicity

The property of an antimicrobial drug that allows it to kill or inhibit microbial targets while causing minimal or no harm to the host.

Cell wall biosynthesis inhibitors

Bactericidal drugs that block peptidoglycan synthesis, making cells susceptible to osmotic lysis (effective because human cells lack peptidoglycan). Examples: penicillins, cephalosporins, monobactams, carbapenems (all beta-lactams), vancomycin (glycopeptide), bacitracin.

Beta-lactam ring

The core structural feature shared by penicillins, cephalosporins, monobactams, and carbapenems; mimics the peptidoglycan subunit recognized by penicillin-binding proteins (PBPs/transpeptidases), blocking crosslinking.

Vancomycin

A glycopeptide that binds directly to peptidoglycan precursor peptide chains, blocking transglycosylation and transpeptidation; narrow-spectrum against gram-positive bacteria only (cannot penetrate gram-negative outer membrane).

Bacitracin

Blocks transport of peptidoglycan precursors across the cytoplasmic membrane; broad-spectrum but nephrotoxic, mainly used topically (e.g., in Neosporin).

Protein synthesis inhibitors (30S subunit)

Target the bacterial 30S ribosomal subunit. Examples: aminoglycosides (bactericidal; cause misreading of codons), tetracyclines (bacteriostatic; block tRNA binding).

Protein synthesis inhibitors (50S subunit)

Target the bacterial 50S ribosomal subunit. Examples: macrolides, lincosamides, chloramphenicol (all bacteriostatic; block peptide bond formation), oxazolidinones (interfere with initiation complex formation).

Membrane function inhibitors

Disrupt bacterial membrane integrity. Examples: polymyxin B and colistin (target gram-negative outer/inner membranes via LPS interaction), daptomycin (targets gram-positive cytoplasmic membrane).

Nucleic acid synthesis inhibitors

Block DNA or RNA synthesis. Examples: rifamycins/rifampin (block RNA polymerase), fluoroquinolones like ciprofloxacin (block DNA gyrase).

Antimetabolites (metabolic pathway inhibitors)

Competitively inhibit bacterial metabolic enzymes. Examples: sulfonamides (block folic acid synthesis via PABA mimicry), trimethoprim (blocks a later step in folic acid synthesis), isoniazid (blocks mycolic acid synthesis in mycobacteria).

Bedaquiline

A diarylquinoline that inhibits mycobacterial ATP synthase; reserved for serious drug-resistant tuberculosis due to toxicity.

Antifungal drug targets

Most commonly disrupt ergosterol (fungal membrane sterol, analogous to human cholesterol) or fungal cell wall/chitin components, exploiting differences from human cells.

imidazoles/triazoles

Inhibit ergosterol biosynthesis. Examples: miconazole, ketoconazole, clotrimazole (imidazoles

Allylamines

Inhibit an earlier step in ergosterol biosynthesis than azoles. Example: terbinafine (topical/oral for dermatophyte and nail infections).

Polyenes

Bind ergosterol directly, creating membrane pores. Examples: nystatin (topical), amphotericin B (systemic fungal infections, nephrotoxic).

Echinocandins

Block synthesis of beta(1→3) glucan in fungal cell walls ("penicillin for fungi"). Example: caspofungin.

Antiprotozoan drug mechanisms

Include antimetabolites, nucleic acid synthesis inhibitors, and heme detoxification inhibitors.

Antimalarial antiprotozoans

Atovaquone (blocks electron transport), proguanil (folic acid synthesis inhibitor, used with atovaquone as Malarone), artemisinin (produces reactive oxygen species), chloroquine/mefloquine/quinacrine (quinolines; inhibit heme detoxification).

Metronidazole/tinidazole

Nitroimidazoles that cause DNA strand breakage in anaerobic protozoans (Giardia, Entamoeba, Trichomonas); metronidazole also used as an antibacterial.

Pentamidine

Interferes with kinetoplast DNA and tRNA function; used for African sleeping sickness and leishmaniasis.

Antihelminthic drug challenge

Helminths are multicellular eukaryotes similar to humans, making selective toxicity difficult to achieve.

Benzimidazoles

Bind helminthic beta-tubulin, blocking microtubule formation and glucose uptake. Examples: mebendazole, albendazole.

Ivermectin

An avermectin that binds invertebrate-specific glutamate-gated chloride channels, causing paralysis/death of worms; used for river blindness, strongyloidiasis, and parasitic insects.

Niclosamide

Inhibits ATP formation/oxidative phosphorylation; used for tapeworm infections.

Praziquantel

Causes calcium influx and paralysis in worms; used for tapeworms and schistosomiasis.

Antiviral drug challenge

Viruses use host cell machinery to replicate, making selective toxicity difficult; many antivirals are nucleoside analogs.

Acyclovir

A guanosine analog activated by viral thymidine kinase; causes DNA chain termination; used for herpesvirus infections.

Ribavirin

A guanosine analog interfering with DNA/RNA synthesis; used for hepatitis C and RSV.

Amantadine/rimantadine

Block viral escape from endosomes (influenza A); resistance has limited their use.

Neuraminidase inhibitors

Block release of influenza virus from infected cells. Examples: oseltamivir (Tamiflu, oral), zanamivir (Relenza, inhaled), peramivir (Rapivab, IV).

HIV antiretroviral drug classes

Reverse transcriptase inhibitors (e.g., AZT/zidovudine, etravirine), protease inhibitors (e.g., ritonavir), integrase inhibitors (e.g., raltegravir), fusion inhibitors (e.g., enfuvirtide), CCR5 antagonists.

Drug resistance

The evolved ability of a microorganism to survive exposure to an antimicrobial drug that would normally inhibit or kill it; accelerated by overuse, misuse, subtherapeutic dosing, and patient noncompliance.

Mechanisms of drug resistance

Include drug modification/inactivation, prevention of cellular uptake/efflux, target modification, target overproduction/enzymatic bypass, and target mimicry.

Drug modification/inactivation

Resistance genes encode enzymes that chemically alter or destroy the drug. Example: beta-lactamases hydrolyze the beta-lactam ring, inactivating beta-lactam drugs.

Efflux pumps

Membrane proteins that actively transport antimicrobial drugs out of the cell, preventing effective accumulation; can confer cross-resistance to multiple drug classes (e.g., beta-lactams, tetracyclines, fluoroquinolones).

Target modification

Structural changes to a drug's target site prevent drug binding. Examples: altered PBPs (beta-lactam resistance), altered ribosomes (macrolide/tetracycline/aminoglycoside resistance), altered DNA gyrase (fluoroquinolone resistance).

Target mimicry

A resistance mechanism where a protein mimics the drug's target, diverting the drug away from its actual target. Example: MfpA protein in Mycobacterium tuberculosis mimics DNA, diverting fluoroquinolones from DNA gyrase.

Multidrug-resistant microbe (MDR/"superbug")

A microbe carrying one or more resistance mechanisms, making it resistant to multiple antimicrobial classes.

Cross resistance

A single resistance mechanism that confers resistance to multiple different antimicrobial drugs (e.g., one efflux pump exporting several drug classes).

ESKAPE pathogens

A group of clinically important, difficult-to-treat superbugs: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.

MRSA (methicillin-resistant Staphylococcus aureus)

Resistant to nearly all beta-lactams via acquisition of a new low-affinity penicillin-binding protein; can be hospital-acquired (HA-MRSA) or community-associated (CA-MRSA).

VRE/VRSA/VISA

Vancomycin-resistant enterococci and S. aureus (target modification of peptidoglycan peptide chains) and vancomycin-intermediate S. aureus (increased vancomycin-trapping targets); treated with drugs like linezolid.

Extended-spectrum beta-lactamases (ESBLs)

Enzymes in gram-negative bacteria that confer resistance to penicillins, cephalosporins, monobactams, and beta-lactamase-inhibitor combinations (but not carbapenems); often plasmid-encoded with multidrug resistance.

Carbapenem-resistant Enterobacteriaceae (CRE)

Gram-negative bacteria resistant to carbapenems via carbapenemase production, efflux, or reduced porin uptake; a major healthcare-associated infection concern.

MDR-TB / XDR-TB

Multidrug-resistant tuberculosis (resistant to rifampin and isoniazid) and extensively drug-resistant tuberculosis (also resistant to fluoroquinolones and a second-line injectable drug).

Clavulanic acid

A beta-lactamase inhibitor (structurally similar to beta-lactams but not itself effective) that is combined with amoxicillin (Augmentin) to protect the antibiotic from being inactivated by beta-lactamases.

Antimicrobial susceptibility testing (AST)

Laboratory testing to determine a drug's spectrum of activity and appropriate therapeutic dosage against a specific organism.

Kirby-Bauer disk diffusion test

A test using antibiotic-impregnated disks placed on an agar plate inoculated with a bacterial lawn; zones of inhibition (measured in mm, compared to a standard chart) indicate susceptibility or resistance, but cannot distinguish bacteriostatic from bactericidal activity or compare drug potency directly.

Minimal inhibitory concentration (MIC)

The lowest concentration of a drug that inhibits visible bacterial growth, determined via dilution tests (macrobroth, microdilution tray, or Etest).

Minimal bactericidal concentration (MBC)

The lowest drug concentration that kills 99.9% or more of the starting bacterial inoculum; determined by subculturing MIC tubes with no visible growth onto drug-free media.

Etest

A method combining disk-diffusion and dilution principles, using a plastic strip with a drug concentration gradient placed on an inoculated agar plate; the MIC is read where an elliptical zone of inhibition intersects the strip's gradient markings.

Antibiogram

A compilation of local antibiotic susceptibility data by bacterial pathogen, used to guide appropriate empiric antimicrobial therapy before lab results are available.