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Medical Microbiology 9e:
Microbiology Exam Study Notes
SECTION 1: BACTERIA
1.1 Structure - Prokaryotes vs. Eukaryotes
Bacteria are prokaryotes - they lack a nucleus, mitochondria, Golgi bodies, and endoplasmic reticulum.
| Feature | Prokaryote (Bacteria) | Eukaryote (Human/Fungi) |
|---|
| Nucleus | No membrane-bound nucleus | True nucleus |
| Ribosome | 70S (50S + 30S subunits) | 80S (60S + 40S) |
| Chromosome | Single, circular, double-stranded DNA | Multiple linear chromosomes |
| Cell wall | Peptidoglycan (except Mycoplasma) | None (animal) or chitin (fungi) |
| Organelles | None | Yes |
Exam tip: The 70S ribosome is the target of many antibiotics (aminoglycosides, tetracyclines, macrolides, chloramphenicol). The 80S ribosome is not affected - that's why these drugs are selective.
1.2 Bacterial Classification
Bacteria are classified by:
- Staining - Gram stain, acid-fast stain
- Morphology - cocci (spheres), rods (bacilli), spirals
- Arrangement - single, chains (strepto-), clusters (staphylo-)
- Metabolism - aerobic, anaerobic, facultative anaerobe
- Genotype - 16S rRNA sequencing (gold standard)
Gram Stain - The Big Distinction
| Gram-Positive | Gram-Negative |
|---|
| Color | Purple (retain crystal violet) | Pink/Red (take up safranin counterstain) |
| Cell wall | Thick peptidoglycan (150-500 Å) | Thin peptidoglycan + outer membrane |
| Teichoic acids | Yes | No |
| LPS (Endotoxin) | No | Yes - major virulence factor |
| Outer membrane | No | Yes (barrier to antibiotics + complement) |
| Periplasmic space | No | Yes (contains beta-lactamases) |
Key gram-positive pathogens: Staphylococcus, Streptococcus, Enterococcus, Bacillus, Clostridium, Listeria
Key gram-negative pathogens: E. coli, Salmonella, Shigella, Klebsiella, Pseudomonas, Neisseria, Haemophilus, Helicobacter
Neither (special cell walls):
- Mycobacterium - acid-fast (waxy mycolic acid wall)
- Mycoplasma - NO cell wall (not targeted by beta-lactams)
- Chlamydia - obligate intracellular
- Rickettsia - obligate intracellular
1.3 Cell Wall Components
Peptidoglycan (Murein)
- Meshlike structure made of glycan chains (GlcNAc + MurNAc) cross-linked by peptide bridges
- Gives rigidity and determines bacterial shape
- Target of beta-lactams (penicillin, cephalosporins) and vancomycin
- Degraded by lysozyme (found in tears and mucus)
- Mycoplasmas have no peptidoglycan - that's why beta-lactams don't work against them
Gram-Positive Extras
- Teichoic acid - strengthens wall, sequesters Ca2+ ions
- Lipoteichoic acid - activates innate host defenses
Gram-Negative Extras
- Outer membrane - lipopolysaccharide (LPS) + phospholipids + proteins
- LPS = Endotoxin - the lipid A portion causes fever, sepsis, and shock
- Periplasmic space - contains enzymes like beta-lactamases
- Outer membrane blocks large/hydrophobic molecules and complement
Other Surface Structures
| Structure | Function |
|---|
| Capsule | Antiphagocytic - protects from complement + phagocytes |
| Pili/Fimbriae | Adhesion to host cells |
| Flagella | Motility |
| Plasmids | Transfer of antibiotic resistance (R factors) |
| Spores | Survival in harsh conditions (Bacillus, Clostridium) |
1.4 Mechanisms of Bacterial Pathogenesis
"To a bacterium, the human body is a collection of environmental niches providing warmth, moisture, and food." - Medical Microbiology 9e
Bacteria cause disease via two main mechanisms:
A. Direct Tissue Damage
- Enzymes: proteases, lipases, hyaluronidase, collagenase
- Type III secretion systems - molecular "needles" inject toxins directly into host cells
B. Toxins
| Type | Location | Properties | Examples |
|---|
| Exotoxin | Secreted by bacteria | Protein, heat-labile, high potency, specific action, immunogenic | Cholera toxin, tetanus toxin, botulinum toxin, diphtheria toxin |
| Endotoxin (LPS) | Gram-negative outer membrane | Lipopolysaccharide, heat-stable, less specific, causes systemic inflammation | All gram-negative bacteria |
Classic exotoxin examples:
- Clostridium tetani - tetanospasmin blocks inhibitory neurotransmitters (spastic paralysis - "lockjaw")
- Clostridium botulinum - botulinum toxin blocks acetylcholine release (flaccid paralysis)
- Vibrio cholerae - cholera toxin (ADP-ribosylates Gs protein → cAMP↑ → rice-water diarrhea)
- Corynebacterium diphtheriae - diphtheria toxin (ADP-ribosylates EF-2 → inhibits protein synthesis)
- Staphylococcus aureus - multiple toxins: TSST-1 (toxic shock), Panton-Valentine leukocidin (PVL)
C. Immune Evasion
- Capsule - blocks opsonization and phagocytosis
- Protein A (S. aureus) - binds IgG Fc, blocks opsonization
- M protein (Streptococcus) - antiphagocytic
- Thick peptidoglycan (gram-positive) - resists complement membrane attack complex
- O antigen on LPS (gram-negative) - limits complement access
D. Virulence Factors - Key Concepts
- Pathogenicity islands - clusters of virulence genes on chromosomes or plasmids, often transferred together (e.g., SPI-2 in Salmonella)
- Quorum sensing - bacteria "count" their numbers; when a threshold is reached, they coordinate virulence factor expression (e.g., Pseudomonas biofilm using N-acyl homoserine lactone)
- Biofilm - protective matrix; highly resistant to antibiotics and immune responses
SECTION 2: VIRUSES
2.1 Basic Properties
- Size: 18-600 nm (most < 200 nm - NOT visible by light microscope)
- Genome: Either DNA or RNA (never both)
- Structure: Nucleic acid + protein capsid (+ lipid envelope in enveloped viruses)
- Obligate intracellular parasites - require host cell machinery to replicate
2.2 Viral Classification
| Property | Categories |
|---|
| Nucleic acid | DNA or RNA |
| Strandedness | Single-stranded (ss) or Double-stranded (ds) |
| Sense (RNA viruses) | Positive (+) sense = reads like mRNA; Negative (-) sense = must make mRNA first |
| Capsid symmetry | Icosahedral, Helical, Complex |
| Envelope | Enveloped or Non-enveloped (naked) |
DNA Viruses (mnemonic: HHAPPPy)
| Family | Example | Disease |
|---|
| Herpesviridae | HSV-1/2, VZV, EBV, CMV, HHV-6/8 | Cold sores, chickenpox, mono, CMV retinitis |
| Hepadnaviridae | Hepatitis B virus | Hepatitis B, hepatocellular carcinoma |
| Adenoviridae | Adenovirus | Respiratory illness, pharyngoconjunctival fever |
| Parvoviridae | Parvovirus B19 | Fifth disease (erythema infectiosum), aplastic crisis |
| Papillomaviridae | HPV | Warts, cervical/anal cancer |
| Polyomaviridae | JC virus, BK virus | PML (JC), nephropathy (BK) in immunocompromised |
| Poxviridae | Smallpox, Molluscum | Smallpox (eradicated), molluscum contagiosum |
RNA Viruses - Selected High-Yield Examples
| Virus | Genome | Envelope | Disease |
|---|
| Influenza | (-) ss RNA | Yes | Flu, reassortment (pandemic) |
| HIV | (+) ss RNA retrovirus | Yes | AIDS |
| Hepatitis C | (+) ss RNA | Yes | Chronic hepatitis |
| Measles | (-) ss RNA | Yes | Measles (Morbillivirus) |
| Rabies | (-) ss RNA | Yes | Rabies (Negri bodies) |
| Rotavirus | ds RNA (segmented) | No | #1 cause of infantile gastroenteritis |
| Poliovirus | (+) ss RNA | No | Polio |
| Norovirus | (+) ss RNA | No | Epidemic gastroenteritis |
| Ebola | (-) ss RNA | Yes | Viral hemorrhagic fever |
2.3 Enveloped vs. Non-Enveloped - Clinical Significance
| Enveloped | Non-Enveloped (Naked) |
|---|
| Stability | Fragile - killed by drying, detergents, heat | More stable in environment |
| Transmission | Requires close contact (secretions, blood) | Fecal-oral, respiratory droplets |
| Alcohol-based sanitizer | Effective | Less effective |
| Examples | HIV, Herpes, Influenza, Hepatitis B/C | Poliovirus, Rotavirus, Norovirus, Parvovirus |
2.4 Viral Replication Steps (General)
- Attachment - viral surface protein binds host receptor
- Entry/Penetration - fusion (enveloped) or receptor-mediated endocytosis
- Uncoating - release of nucleic acid
- Replication - using host machinery; RNA viruses replicate in cytoplasm (exception: influenza, retroviruses in nucleus)
- Assembly - new virions assembled
- Release - budding (enveloped) or cell lysis (naked)
2.5 Mechanisms of Viral Disease
- Direct cytopathic effect - virus destroys the cell it infects
- Immune-mediated damage - host inflammatory response causes tissue damage (can be the primary cause of symptoms)
- Chronic infection / latency - virus persists (e.g., HSV latent in ganglia; VZV reactivates as shingles)
- Oncogenic transformation - viral genes integrate and cause cancer (HPV → cervical cancer; EBV → Burkitt lymphoma; HBV/HCV → hepatocellular carcinoma)
- Immunosuppression - HIV destroys CD4+ T cells; CMV in immunocompromised
SECTION 3: FUNGI
3.1 Basic Properties
- Eukaryotes - have nucleus, mitochondria, Golgi, ER
- Cell wall contains chitin (not peptidoglycan)
- Cell membrane contains ergosterol (not cholesterol) - target of antifungals
- Two morphological forms:
- Yeast - unicellular, reproduce by budding
- Mold (Hyphae) - filamentous, reproduce sexually and asexually
3.2 Dimorphic Fungi - High Yield!
Dimorphic fungi = mold in environment, yeast in body (37°C)
Mnemonic: "Mold in cold, Yeast in heat"
| Organism | Endemic Region | Disease |
|---|
| Histoplasma capsulatum | Mississippi/Ohio River valleys; bird/bat droppings | Histoplasmosis (flu-like illness, can disseminate) |
| Blastomyces dermatitidis | Midwest/Southeast US | Blastomycosis (pulmonary + skin) |
| Coccidioides immitis | Southwestern US, California | Coccidioidomycosis ("Valley fever") |
| Paracoccidioides brasiliensis | Central/South America | Paracoccidioidomycosis |
| Sporothrix schenckii | Soil, rose thorns | Sporotrichosis (lymphocutaneous) |
3.3 Major Fungal Pathogens
| Organism | Form | Key Features | Disease |
|---|
| Candida albicans | Yeast (+ pseudohyphae) | Germ tube test positive; most common fungal infection | Thrush, vaginitis, candidemia (immunocompromised) |
| Cryptococcus neoformans | Yeast | India ink - capsule visible; urease positive; pigeon droppings | Meningitis (HIV/AIDS) |
| Aspergillus fumigatus | Mold (hyphae) | 45° branching septate hyphae | Allergic bronchopulmonary aspergillosis, invasive aspergillosis |
| Mucor/Rhizopus | Mold | 90° (right angle) non-septate hyphae | Mucormycosis (rhinocerebral in diabetics/immunocompromised) |
| Pneumocystis jirovecii | Atypical (not classic yeast/mold) | Silver stain; doesn't respond to antifungals | PCP pneumonia (AIDS patients, CD4 <200) |
3.4 Antifungal Drug Targets
| Drug Class | Mechanism | Examples |
|---|
| Polyenes | Bind ergosterol → membrane disruption | Amphotericin B, Nystatin |
| Azoles | Inhibit ergosterol synthesis (CYP450) | Fluconazole, Itraconazole, Voriconazole |
| Echinocandins | Inhibit beta-glucan synthesis (cell wall) | Caspofungin, Micafungin |
| Flucytosine | Inhibits DNA/RNA synthesis | 5-FC (used with Amphotericin B for Cryptococcus) |
SECTION 4: PARASITES
4.1 Overview
- Most complex microbes - eukaryotes, unicellular to multicellular
- Range from 4-5 μm protozoa to 10-meter tapeworms
- Complex life cycles; often require multiple hosts
- Geographic distribution is key to diagnosis (travel history!)
4.2 Classification
Protozoa (Unicellular)
| Organism | Transmission | Disease |
|---|
| Plasmodium spp. | Anopheles mosquito | Malaria (P. falciparum = most severe) |
| Toxoplasma gondii | Cat feces, undercooked meat | Toxoplasmosis (brain abscess in AIDS; congenital infection) |
| Entamoeba histolytica | Fecal-oral (contaminated water) | Amoebic dysentery, liver abscess |
| Giardia lamblia | Fecal-oral (contaminated water) | Giardiasis (malabsorption, fatty diarrhea) |
| Trypanosoma cruzi | Reduviid (kissing) bug feces | Chagas disease (cardiomyopathy) |
| Trypanosoma brucei | Tsetse fly | African sleeping sickness |
| Leishmania spp. | Sandfly | Cutaneous, mucocutaneous, visceral leishmaniasis |
| Trichomonas vaginalis | Sexual contact | Vaginitis (frothy discharge) |
Helminths (Worms)
Nematodes (Roundworms)
| Organism | Route | Disease |
|---|
| Ascaris lumbricoides | Fecal-oral | Intestinal obstruction |
| Strongyloides stercoralis | Skin penetration | Hyperinfection in immunocompromised |
| Necator/Ancylostoma | Skin penetration | Hookworm, iron deficiency anemia |
| Trichinella spiralis | Undercooked pork | Trichinellosis (myositis, periorbital edema) |
| Wuchereria bancrofti | Mosquito | Lymphatic filariasis (elephantiasis) |
Cestodes (Tapeworms)
| Organism | Route | Disease |
|---|
| Taenia solium (pork) | Ingestion of cysts | Neurocysticercosis (seizures!) |
| Echinococcus | Dog feces | Hydatid cyst (liver) |
| Diphyllobothrium latum | Raw fish | Vitamin B12 deficiency |
Trematodes (Flukes)
| Organism | Route | Disease |
|---|
| Schistosoma spp. | Skin penetration (water) | Portal hypertension, bladder cancer (S. haematobium) |
| Clonorchis sinensis | Raw fish | Cholangiocarcinoma |
QUICK REFERENCE - HIGH-YIELD MNEMONICS
| Mnemonic | Meaning |
|---|
| "Be Very Nasty, You Foolish Person" | Gram-negative rod lactose fermenters: E. coli, Klebsiella, Enterobacter (YES) vs non-fermenters (Pseudomonas, Proteus) |
| "Stay PURE" | Spore-forming bacteria: Bacillus anthracis, Clostridium (aerobic spores vs. anaerobic spores) |
| "Mold in Cold, Yeast in Heat" | Dimorphic fungi - mold form in environment, yeast form in body |
| "Cholera = Comma" | Vibrio cholerae is comma-shaped |
| "HACEK" | Endocarditis-causing gram-negative organisms: Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella |
| "Please Don't Give Me Cash" | Obligate intracellular bacteria: Rickettsia, Coxiella, Chlamydia, Brucella, Mycobacterium leprae, Listeria (some) |
| "Staph Aureus = Always, Suspect" | MRSA, TSST-1, PVL toxin, protein A (immune evasion) |
LAST-MINUTE FACTS TO REMEMBER
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Gram stain exceptions: Mycobacteria (acid-fast), Treponema (too thin - use dark-field microscopy), Rickettsia/Chlamydia (intracellular, can't be Gram stained easily)
-
Cell wall targets: Beta-lactams and vancomycin target gram-positive cell wall synthesis; vancomycin is the last resort for MRSA
-
LPS = endotoxin = gram-negative = causes fever, hypotension, septic shock via IL-1, IL-6, TNF-alpha
-
Exotoxin vs. Endotoxin: Exotoxins are proteins (can be inactivated/made into toxoids for vaccines - tetanus, diphtheria); endotoxins are lipopolysaccharide and cannot be toxoided
-
HIV attacks CD4+ T cells (helper T cells) - when CD4 < 200 cells/μL = AIDS; susceptible to opportunistic infections (PCP, Cryptococcus, Toxoplasma, CMV, MAC)
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Fungal cell membrane = ergosterol (target of polyenes and azoles) vs. human cell membrane = cholesterol
-
Biofilm - Pseudomonas and Staphylococcus are notorious for forming biofilms on prosthetics/catheters; highly antibiotic resistant
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