Comprehensive Study Notes: Antimicrobial Drugs, Microbial Diseases, and Host Systems

Antimicrobial Drugs and Their Mechanisms

Key Definitions

• Selective toxicity: The ability of a drug to target and kill or inhibit harmful microorganisms without causing significant damage to the host’s cells.

• Chemotherapy: The use of chemicals to treat disease, especially infections and cancer.

• Antibiotic: A substance produced by a microbe that, in small amounts, inhibits another microbe.

• Antimicrobial drugs: Synthetic substances that interfere with the growth of microbes.

Penicillin and Its Source

• Penicillin: An antibiotic medication used to treat bacterial infections by preventing the synthesis of peptidoglycan, an essential component of bacterial cell walls.

• Source: Produced by the fungus Penicillium.

• Kingdom: Fungi.

Bactericidal vs. Bacteriostatic

• Bactericidal: Kills bacteria directly.

• Bacteriostatic: Inhibits the growth and reproduction of bacteria without killing them outright.

Major Action Modes of Antibacterial Drugs

Antibacterial drugs act through several major mechanisms to inhibit or kill bacteria:

• Inhibition of cell wall synthesis (e.g., penicillins, cephalosporins, bacitracin, vancomycin)

• Inhibition of protein synthesis (e.g., chloramphenicol, erythromycin, tetracyclines, streptomycin)

• Inhibition of nucleic acid replication and transcription (e.g., quinolones, rifampin)

• Injury to plasma membrane (e.g., polymyxin B)

• Inhibition of essential metabolite synthesis (e.g., sulfanilamide, trimethoprim)

Penicillinase

• Penicillinase: An enzyme produced by certain bacteria (e.g., Staphylococcus) that breaks open the β-lactam ring of penicillin, rendering the antibiotic ineffective.

Sulfonamides and Drug Synergism

• Sulfonamides: Bacteriostatic synthetic antibiotics that inhibit bacterial growth by interfering with folic acid synthesis.

• Drug synergism: The combination of trimethoprim and sulfamethoxazole (TMP-SMZ) is an example, where the drugs work together to produce a stronger effect than either alone.

Folic Acid in Cellular Metabolism

• Folic acid: An enzyme cofactor required for the synthesis of proteins, DNA, and RNA in all cellular organisms.

• Humans: Obtain folic acid from diet (fortified foods, supplements, leafy greens).

• Bacteria: Must synthesize folic acid de novo, making the pathway a target for selective toxicity.

Selective Toxicity in Antifungal and Antiviral Drugs

• Antifungal drugs: Fungi are eukaryotes like humans, so there are fewer unique targets for drugs, making selective toxicity harder to achieve.

• Antiviral drugs: Viruses rely on host cell machinery, so there are very few safe and effective drug targets, resulting in fewer antiviral drugs.

Acyclovir and Viral Replication

• Acyclovir: An antiviral drug that mimics deoxyguanosine, is incorporated into viral DNA, and causes premature chain termination, blocking viral replication.

Kirby-Bauer Test

• Kirby-Bauer test: A laboratory method using agar plates to determine the susceptibility of microbes to antibiotics by measuring zones of inhibition.

Mechanisms of Antibiotic Resistance

• Bacteria can become resistant to antibiotics through several mechanisms:

• Blocking entry: Preventing the antibiotic from entering the cell.

• Inactivation by enzymes: Enzymatic destruction or modification of the drug (e.g., penicillinase).

• Alteration of target molecule: Modifying the drug’s target so the antibiotic cannot bind effectively.

• Efflux of antibiotic: Pumping the antibiotic out of the cell before it can act.

Development of Antibiotic Resistance

• Antibiotic resistance can develop during therapy, especially if not all bacteria are killed and resistant mutants survive and proliferate.

• Resistance is measured by the amount of antibiotic needed to control bacterial growth.

Misuse of Antibiotics

• Misuse includes underdosing, not completing prescribed courses, or using antibiotics for viral infections, all of which promote resistance.

Drug Synergism vs. Antagonism

• Synergism: Two drugs together produce a stronger effect than either alone.

• Antagonism: One drug reduces or blocks the effect of another drug.

Microbial Diseases of the Skin and Eyes

Skin as a Barrier

• The skin is salty, dry, and has a low pH, which limits microbial growth.

Lysozyme

• Lysozyme: An enzyme that hydrolyzes peptidoglycan, breaking bacterial cell walls and providing innate defense.

Key Terms: Exanthem and Enanthem

• Exanthem: External skin rash.

• Enanthem: Rash on mucous membranes (internal).

Staphylococcal and Streptococcal Infections

• Folliculitis: Superficial infection of hair follicle.

• Sty (stye): Infected eyelash follicle.

• Furuncle (boil): Deeper infection of hair follicle.

• Carbuncle: Hard, deep inflammation under the skin.

• MRSA: Methicillin-resistant Staphylococcus aureus.

• HA-MRSA: Healthcare-associated MRSA.

• CA-MRSA: Community-associated MRSA.

• GAS: Group A Streptococcus, can cause necrotizing fasciitis ("flesh-eating disease").

Acne and Its Treatment

• Genus: Cutibacterium (Propionibacterium) acnes.

• Sebum: Oily substance produced by sebaceous glands.

• Treatments: Antibiotics, benzoyl peroxide, blue light therapy.

Viral and Fungal Skin Diseases

• Warts: Caused by human papillomavirus (HPV-16).

• Smallpox: Caused by variola virus, transmitted via bloodstream, nearly eliminated by vaccination (Edward Jenner).

• Shingles: Reactivation of varicella-zoster virus, latent in dorsal root ganglia.

• MMR vaccine: Protects against measles, mumps, rubella.

• Ringworm and athlete's foot: Fungal infections.

• Thrush: Fungal infection caused by Candida albicans (Kingdom: Fungi).

• Pediculosis: Lice infestation caused by Pediculus humanus capitis (Kingdom: Animalia).

Ophthalmia Neonatorum Prevention

• Newborns receive eye drops with silver nitrate or antibiotics to prevent serious eye infection (ophthalmia neonatorum).

Microbial Diseases of the Nervous System

Central and Peripheral Nervous Systems

• CNS: Brain and spinal cord.

• PNS: Nerves branching from CNS.

• Cerebrospinal fluid: Liquid cushioning the brain and spinal cord.

Key Terms: Meningitis, Encephalitis, Meningoencephalitis

• Meningitis: Inflammation of the meninges.

• Encephalitis: Inflammation of the brain.

• Meningoencephalitis: Inflammation of both meninges and brain.

Spinal Tap (Lumbar Puncture)

• Needle inserted into lumbar region to collect cerebrospinal fluid for testing or to deliver medications.

Bacterial and Viral Nervous System Diseases

• Tetanus: Caused by Clostridium tetani, produces a neurotoxin.

• Botulism: Caused by Clostridium botulinum (exotoxin), associated with improperly canned foods; botox is a medical use of the toxin.

• Polio: Caused by poliovirus, enters via CNS, controlled by vaccination.

• Rabies: Transmitted via animal bites, affects nervous system, mutates easily.

• Cryptococcus neoformans: Fungal (yeast), enters via respiratory route.

• Trypanosoma brucei: Parasitic protozoan, transmitted by arthropod vector.

• Naegleria fowleri: Protozoan parasite, enters through nose (contaminated water), causes Primary Amoebic Meningoencephalitis (PAM).

Microbial Diseases of the Cardiovascular and Lymphatic Systems

Key Terms

• Septicemia: Acute illness due to pathogens or their toxins in the blood.

• Sepsis: Systemic inflammatory response syndrome (SIRS).

• Lymphangitis: Inflamed lymph vessels.

• Septic shock: Sepsis with uncontrollable decreased blood pressure.

Gram-Negative vs. Gram-Positive Sepsis

• Gram-negative sepsis: Endotoxic shock due to lipopolysaccharides (LPS).

• Gram-positive sepsis: Exotoxic shock, often hospital-acquired, associated with exotoxins.

Other Cardiovascular Diseases

• Endocarditis: Inflammation of the endocardium.

• Pericarditis: Inflammation of the sac around the heart.

• Brucellosis: Caused by Brucella, transmitted via milk, causes undulant fever.

• Anthrax: Caused by Bacillus anthracis, transmitted via infected animals.

• Gas gangrene: Caused by Clostridium perfringens, treated with antibiotics and oxygen therapy.

• Cat-scratch disease: Caused by Bartonella henselae.

• Plague (Black Death): Caused by Yersinia pestis, transmitted by rat flea.

• Lyme disease: Caused by Borrelia burgdorferi, transmitted by ticks, prevalent in the Northeast USA.

• Typhus: Caused by Rickettsia species, transmitted by arthropod vectors.

• Mononucleosis: Caused by Epstein-Barr virus, transmitted via saliva.

• Ebolavirus: Damages blood vessels, causes internal/external bleeding, high mortality.

• Toxoplasmosis: Caused by Toxoplasma gondii (Kingdom: Protista), cats are definitive hosts.

• Malaria: Caused by Plasmodium vivax, transmitted by mosquitoes.

Microbial Diseases of the Respiratory System

Upper vs. Lower Respiratory Tract

• Upper respiratory tract: Nose, pharynx, middle ear, saliva, tears.

• Lower respiratory tract: Larynx, trachea, bronchial tubes, alveoli.

Key Terms

• Pharyngitis: Sore throat, inflammation of throat mucous membranes.

• Laryngitis: Inflammation affecting speech.

• Sinusitis: Inflammation of sinus mucous membranes.

• Epiglottitis: Life-threatening inflammation of the epiglottis.

Common Respiratory Diseases

• Strep throat and Scarlet fever: Caused by Streptococcus pyogenes.

• Common cold: Caused by viruses; antibiotics are ineffective.

• Pertussis (whooping cough): Caused by Bordetella pertussis, prevented by DTaP vaccine.

• Tuberculosis: Caused by Mycobacterium tuberculosis, diagnosed by skin test, blood test, x-ray, or CT.

• Influenza: Caused by influenzavirus (RNA genome), symptoms include chills, fever, headache, muscle aches; hemagglutinin (HA) spikes attach to host cells, neuraminidase (NA) spikes help virus release.

• Fungal respiratory infections: Histoplasma capsulatum (histoplasmosis), Coccidioides immitis (coccidioidomycosis), Pneumocystis jirovecii (pneumonia).

Microbial Diseases of the Digestive System

Digestive System Structure

• GI tract: Mouth, pharynx, esophagus, stomach, small and large intestine.

• Accessory structures: Teeth, tongue, salivary glands, liver, gallbladder, pancreas.

Microbial Survival in the Digestive Tract

• Few microbes survive in the stomach due to high acidity.

• Bacteria in the large intestine are mostly anaerobic.

• There are about 100 billion bacterial cells per gram of feces.

Common Digestive Diseases

• Dental caries: Caused by Streptococcus mutans, which converts sucrose to lactic acid, dissolving tooth enamel.

• Shigellosis: Caused by Shigella, treated with fluoroquinolones and rehydration.

• Salmonellosis: Caused by Salmonella enterica, associated with chicken eggs, causes fever, nausea, cramps.

• Cholera: Caused by Vibrio cholerae, leads to dehydration and shock.

• Helicobacter Peptic Ulcers: Caused by Helicobacter pylori, forms ulcers in the stomach lining.

• Hepatitis: Inflammation of the liver, caused by Hepatitis A-E viruses, transmitted via various routes.

• Aflatoxin poisoning: Caused by Aspergillus flavus, associated with peanuts.

• Protozoan diseases: Giardiasis (Giardia intestinalis), Cryptosporidiosis (Cryptosporidium), Amebiasis (Entamoeba histolytica).

• Ophthalmic cysticercosis: Caused by Taenia solium (tapeworm, Kingdom: Animalia).

Tapeworm Life Cycle

• Adult tapeworms release eggs, which are ingested by intermediate hosts (e.g., deer, sheep).

• Larvae migrate to tissues and form hydatid cysts.

• Definitive hosts (e.g., dogs) ingest cysts, completing the cycle.

Trichinella spiralis Life Cycle

• Ingested cysts develop into adults in the intestine of pigs or humans.

• Larvae encyst in muscle tissue.

• Humans acquire infection by eating undercooked pork containing cysts.

Microbial Diseases of the Urinary and Reproductive Systems

Organs of the Urinary and Reproductive Systems

• Urinary system: Kidneys, ureters, urinary bladder, urethra.

• Female reproductive system: Ovaries, uterine tubes, uterus, cervix, vagina, external genitalia.

• Male reproductive system: Testes, epididymis, vas deferens, seminal vesicles, prostate, penis, urethra.

Sterile Regions and Normal Flora

• Urinary bladder, upper urinary tract, and male urethra are usually sterile.

• Vaginal flora includes Lactobacilli, Streptococci, and yeast (Candida albicans).

Key Terms

• Urethritis: Inflammation of the urethra.

• Cystitis: Inflammation of the bladder.

• Ureteritis: Infection of the ureters.

• Pyelonephritis: Inflammation of one or both kidneys.

Common Urinary and Reproductive Diseases

• Gonorrhea: Caused by Neisseria gonorrhoeae; symptoms include painful urination and pus in men, pelvic inflammatory disease in women; untreated can lead to endocarditis, meningitis, arthritis.

• Genital herpes: Caused by herpes simplex virus type 2 (HSV-2); symptoms include painful vesicles and urination.