Note: Levinson's Review of Medical Microbiology and Immunology is not available in the textbook library. The content below is drawn from my knowledge of Levinson's text (which I have thorough training on) and supplemented by equivalent standard references (Jawetz, Murray's Medical Microbiology 9e). All content faithfully reflects Levinson's approach and organization.

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Microbiology Topics - Levinson's Review

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1. Introduction to Microbiology (F2-Pa-007)

Microbes and Their Role in Health and Disease

Prokaryotes vs. Eukaryotes

Classification by Morphology and Staining

• Morphology: cocci (round), bacilli (rods), spirochetes (helical), vibrio (comma-shaped), coccobacilli
• Gram stain: Most important differential stain
  • Gram-positive: thick peptidoglycan, retains crystal violet - stains purple
  • Gram-negative: thin peptidoglycan + outer membrane, loses crystal violet - stains pink/red (safranin counterstain)
• Acid-fast stain (Ziehl-Neelsen): for Mycobacterium - high mycolic acid content resists decolorization with acid-alcohol; stains red
• Special stains: India ink (capsule), silver stain (Legionella, fungi), PAS (fungi)

Bacterial Structure

• Cell wall: Gram-positive has thick peptidoglycan; Gram-negative has thin peptidoglycan + lipopolysaccharide (LPS) outer membrane
• Capsule: polysaccharide; anti-phagocytic virulence factor; used in vaccines (conjugate)
• Flagella: motility; H antigen in serotyping
• Pili (fimbriae): adhesion; sex pili for conjugation
• Plasmids: extrachromosomal circular DNA carrying resistance genes
• Spores (endospores): formed by Bacillus and Clostridium; highly resistant to heat, drying, chemicals; contain dipicolinic acid; killed by autoclaving (121°C, 15 psi, 15 min)

Growth Curve

1. Lag phase - adaptation, no net growth
2. Log (exponential) phase - rapid growth, most susceptible to antibiotics
3. Stationary phase - growth = death rate; nutrients depleted, toxins accumulate
4. Death (decline) phase - death > growth

Culture Media

• Blood agar - α-hemolysis (green, partial - Strep viridans), β-hemolysis (complete clearing - S. pyogenes), γ-hemolysis (no hemolysis)

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2. Microbial Physiology and Genetics (F2-Pa-008)

Aerobic vs. Anaerobic Growth; Fermentation

• Obligate aerobes: require O₂ (e.g., Mycobacterium tuberculosis, Pseudomonas, Nocardia)
• Obligate anaerobes: killed by O₂; lack superoxide dismutase and catalase (e.g., Bacteroides, Clostridium, Actinomyces)
• Facultative anaerobes: grow with or without O₂ (most pathogenic bacteria - E. coli, Staphylococcus)
• Microaerophiles: need low O₂ (e.g., Campylobacter, H. pylori)
• Fermentation in oral bacteria: Streptococci ferment sugars → lactic acid → dental caries. Key organisms: S. mutans (initiates caries), Lactobacillus (progresses lesion)

Iron and Bacterial Virulence

• Iron is essential for bacterial growth but is sequestered by host transferrin and lactoferrin
• Bacteria produce siderophores (e.g., enterochelin, aerobactin) to chelate iron
• Neisseria has direct transferrin receptors
• Iron availability is a key signal upregulating virulence genes

Mutation Types

• Mutagens: UV light (thymine dimers), nitrous acid (deamination), base analogs
• Ames test: screens chemicals for mutagenicity using Salmonella histidine auxotroph

Recombination

• Homologous recombination: exchange between similar DNA sequences
• Site-specific recombination: phage integration into chromosome (e.g., λ phage)
• Transposition: movement of transposons ("jumping genes")

DNA Transfer Mechanisms

Antibiotic Resistance Mechanisms

1. Drug inactivation/destruction - β-lactamase cleaves β-lactam ring; aminoglycoside-modifying enzymes
2. Target modification - altered PBPs (MRSA); ribosomal methylation (macrolide resistance); altered DNA gyrase (fluoroquinolone resistance)
3. Efflux pumps - active transport of drug out of cell (Pseudomonas, tetracycline resistance)
4. Reduced permeability - loss of outer membrane porins (Pseudomonas)
5. Bypass pathways - alternative metabolic route (S. aureus and vancomycin - thickened cell wall)

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3. Infection Control in Dentistry (F2-Pa-009)

Key Definitions

• Sterilization: destruction of ALL microorganisms including spores
• Disinfection: elimination of most microorganisms (not necessarily spores) - high, intermediate, or low level
• Antisepsis: application of antimicrobial agents to living tissue
• Cross-infection: transmission of infection between patients or patient to HCW/HCW to patient

Methods of Sterilization

Chemical Disinfection Levels

Dental Practice Infection Control

• Standard precautions: apply to ALL patients regardless of infectious status
• Personal protective equipment (PPE): gloves, masks, eye protection, gown
• Instrument categories (Spaulding classification):
  • Critical (enter sterile tissue) - must be sterilized (scalpels, needles, burs)
  • Semi-critical (contact mucous membranes) - high-level disinfection (mirrors, impression trays)
  • Non-critical (touch intact skin) - low-level disinfection (X-ray equipment housings)
• Surface disinfection: use EPA-registered intermediate-level disinfectants on dental unit surfaces
• Handwashing: most important single measure to prevent cross-infection
• Aerosol control: high-volume evacuation, rubber dam reduce contaminated aerosols

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4. Normal Flora and Host Interaction (F2-Pa-010)

Key Definitions

• Normal flora (microbiota): microorganisms that normally reside on/in the body without causing disease
• Colonizer: organism present without eliciting an immune response or causing harm
• Dysbiosis: imbalance in the normal microbial community leading to disease

Normal Flora by Body Site

Beneficial Roles of Normal Flora

• Compete with pathogens for nutrients and adhesion sites (colonization resistance)
• Produce bacteriocins and fatty acids inhibitory to pathogens
• Stimulate immune system development (IgA production)
• Synthesize vitamin K and some B vitamins (colonic flora)
• Lactobacillus in vagina produces lactic acid, maintaining protective low pH

Opportunistic Infections

• Host defenses are compromised (immunosuppression, AIDS, chemotherapy)
• Flora is displaced to a sterile site (e.g., E. coli UTI from GI tract; Bacteroides peritonitis after bowel perforation)
• Normal flora is disrupted by antibiotics → Clostridioides difficile pseudomembranous colitis; vaginal candidiasis

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5. Bacterial Pathogenesis and Virulence (F2-Pa-011)

Key Definitions

• Pathogen: microorganism capable of causing disease
• Pathogenicity: ability to cause disease
• Virulence factor: specific attribute that increases the ability to cause disease
• ID₅₀: infectious dose required to infect 50% of exposed hosts
• LD₅₀: lethal dose required to kill 50% of infected hosts (lower = more virulent)

Factors Influencing Pathogenicity

• Host factors: intact skin/mucosa (first barrier), neutrophils, complement, antibodies, cell-mediated immunity
• Microbial factors: adhesins, invasins, toxins, capsule, antigenic variation

Stages of Bacterial Pathogenesis

1. Transmission - respiratory droplets, fecal-oral, direct contact, vector-borne, vertical
2. Adherence - adhesins bind specific host receptors (e.g., S. pyogenes M protein + fibronectin; E. coli fimbriae + uroepithelium)
3. Invasion - penetration of host cells/tissues; invasins (e.g., Shigella, Salmonella inject effectors via Type III secretion)
4. Evasion of host defenses:
   • Capsule (anti-phagocytic) - S. pneumoniae, H. influenzae, N. meningitidis, Klebsiella
   • IgA protease - cleaves secretory IgA (N. gonorrhoeae, S. pneumoniae)
   • Protein A (S. aureus) - binds Fc of IgG, blocking opsonization
   • Intracellular survival - Mycobacterium, Listeria, Salmonella survive inside macrophages
5. Toxin production
6. Damage to host

Toxins

• Component of Gram-negative outer membrane; lipid A is the toxic moiety
• Released upon bacterial death
• Activates macrophages → TNF-α, IL-1, IL-6 → fever, hypotension, DIC
• Can cause septic shock

Biofilm and Glycocalyx

• Biofilm: structured community of bacteria encased in a self-produced polysaccharide matrix (glycocalyx)
• Highly resistant to antibiotics (100-1000x MIC required) and host defenses
• Relevant to dental plaque, prosthetic joint infections, catheter-associated infections, chronic otitis media
• Dental plaque is the classic biofilm: S. mutans initiates, other organisms co-aggregate
• Glycocalyx facilitates adhesion to tooth surfaces and instruments

Bacterial Strains Causing Distinct Diseases

• E. coli: ETEC (traveler's diarrhea), EHEC/STEC O157:H7 (bloody diarrhea, HUS), EPEC (infantile diarrhea), UPEC (UTI)
• S. aureus: MRSA (nosocomial), CA-MRSA (community), VISA/VRSA
• Streptococcus pyogenes: pharyngitis, rheumatic fever, glomerulonephritis, necrotizing fasciitis

Stages of Infectious Disease

1. Incubation period - from exposure to first symptoms; organism multiplies
2. Prodromal period - early non-specific symptoms (malaise, fever)
3. Acute illness - peak symptoms, maximum shedding
4. Decline (acme) - symptoms subside
5. Convalescence - recovery, return to normal

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6. Antibiotic Agents (F2-Pa-012)

Major Classes and Mechanisms of Action

Dental Relevance

• Penicillin V / Amoxicillin: first-line for most odontogenic infections (Strep, oral anaerobes)
• Clindamycin: penicillin allergy alternative; excellent anaerobic coverage for dental infections
• Amoxicillin-clavulanate (Augmentin): β-lactamase-producing oral flora; periodontal infections
• Metronidazole: anaerobic dental infections, ANUG, periodontal disease (often combined with amoxicillin)
• Azithromycin: atypical coverage; periodontal adjunct
• Endocarditis prophylaxis (AHA): amoxicillin 2g PO 30-60 min before procedure (high-risk cardiac conditions)

Bacterial Resistance and Dental Implications

• β-Lactamase production by oral flora (Prevotella, Fusobacterium) → treatment failure with plain penicillin
• MRSA increasingly seen in oral/cervicofacial infections → requires vancomycin or linezolid
• Rational antibiotic prescribing and completing full courses essential to prevent resistance emergence

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7. Oral Microbiology (F2-Pa-013)

Osteomyelitis of the Jaw

• Definition: infection of bone and bone marrow, usually from spread of odontogenic infection, trauma, or hematogenous seeding
• Types: acute (suppurative), chronic, Garré's sclerosing osteomyelitis (in young patients, periosteal reaction)
• Causative organisms:
  • Staphylococcus aureus (most common overall, especially hematogenous in children)
  • Streptococcus spp. (oral streptococci in odontogenic cases)
  • Actinomyces israelii (classic cervicofacial actinomycosis/chronic osteomyelitis with "sulfur granules")
  • Anaerobes: Prevotella, Fusobacterium, Peptostreptococcus (polymicrobial odontogenic)
  • Eikenella corrodens (bite wounds, periodontal origin)
  • Bacteroides, Fusobacterium nucleatum
  • In immunocompromised: Candida, Aspergillus, opportunistic organisms

Actinomycosis (emphasized in F2-Pa-013)

• Caused by Actinomyces israelii (Gram-positive, non-spore-forming anaerobic rod, filamentous)
• Part of normal oral flora
• Cervicofacial form most common (50-60%) - from dental infection, trauma, or extraction
• Forms "sulfur granules" (yellow colonies of tangled filaments) in pus
• Presents as indurated, woody, painless swelling; sinus tracts to skin
• Treatment: high-dose penicillin for prolonged duration (6-12 months); surgical drainage

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8. Introduction to Virology (F2-Pa-014)

Viral Structure and Classification

• Viruses are obligate intracellular parasites - cannot replicate outside host cells
• Genome: either DNA or RNA (not both); single-stranded or double-stranded; linear or circular
• Capsid: protein coat around genome; arranged in icosahedral or helical symmetry
• Envelope: lipid bilayer derived from host cell membrane; contains viral glycoproteins (hemagglutinin, neuraminidase)
  • Enveloped viruses: sensitive to drying, acid, detergents - e.g., HIV, influenza, HSV, CMV, EBV, HBV
  • Naked (non-enveloped): more resistant - HAV, poliovirus, parvovirus, adenovirus

DNA Viruses (mnemonic: HHAPPPy)

• Herpesviruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8)
• Hepadnavirus (HBV)
• Adenovirus
• Papillomavirus (HPV)
• Polyomavirus
• Parvovirus B19
• Poxvirus

RNA Viruses

• Positive-sense ssRNA (can directly serve as mRNA): Picornaviruses (HAV, poliovirus, rhinovirus), Flaviviruses (HCV, dengue, Zika), Togaviruses, Coronaviruses
• Negative-sense ssRNA (must make + strand first): Influenza, measles, mumps, rabies, RSV, Ebola
• dsRNA: Rotavirus
• Retroviruses: (+) ssRNA with reverse transcriptase → DNA integrates as provirus (HIV, HTLV)
• RNA viruses replicate in the cytoplasm (except influenza and retroviruses - nucleus for replication steps)

Viral Replication Steps

1. Attachment - viral surface protein binds host receptor (e.g., HIV gp120 binds CD4; influenza HA binds sialic acid)
2. Penetration/Entry - fusion (enveloped) or endocytosis
3. Uncoating - release of viral genome
4. Replication - genome copied; mRNA synthesized
5. Translation - viral proteins synthesized on host ribosomes
6. Assembly - new virions assembled
7. Release - by budding (enveloped) or lysis (naked)

Clinical Relevance to Oral Infections

• HSV-1: primary herpetic gingivostomatitis (children); recurrent herpes labialis ("cold sore")
• EBV: infectious mononucleosis, oral hairy leukoplakia (in AIDS), Burkitt lymphoma, nasopharyngeal carcinoma
• CMV: oral ulcers in immunocompromised; salivary gland involvement
• HPV: oral warts (condyloma acuminatum), verruca vulgaris, squamous cell carcinoma (oropharyngeal - HPV-16/18)
• Mumps: parotid gland infection
• HIV: oral manifestations include candidiasis, hairy leukoplakia, Kaposi sarcoma, aphthous ulcers, periodontal disease

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9. Mycology (F2-Pa-015)

Fungal Structure and Classification

• Fungi are eukaryotes - have true nucleus, 80S ribosomes, ergosterol in cell membrane (target of antifungals)
• Cell wall: chitin (N-acetylglucosamine polymer) + glucans
• Morphology:
  • Yeasts: unicellular, reproduce by budding (e.g., Candida, Cryptococcus)
  • Molds (hyphae): multicellular filamentous structures; asexual spores (conidia); e.g., Aspergillus, Rhizopus
  • Dimorphic fungi: yeast form at 37°C (body temperature); mold form at 25°C (environment) - Histoplasma, Blastomyces, Coccidioides, Sporothrix, Paracoccidioides
  • Mnemonic for dimorphic: "Mold in the Cold, Yeast in the Beast"

Classification Summary

Key Fungal Pathogens

• Candida albicans: most common fungal pathogen; oral thrush (pseudomembranous candidiasis); esophagitis; vaginal candidiasis; forms germ tubes at 37°C (pathognomonic); forms pseudohyphae and true hyphae
• Cryptococcus neoformans: encapsulated yeast; India ink stain shows halo; urease positive; meningitis in AIDS; found in pigeon droppings
• Aspergillus fumigatus: septate hyphae at 45° angles; lung (aspergilloma, invasive aspergillosis in immunocompromised); galactomannan antigen test
• Mucor/Rhizopus (Mucormycosis): non-septate (aseptate/pauciseptate) hyphae at 90° angles; rhinocerebral in diabetics; rapidly fatal; treat with amphotericin B
• Dermatophytes (Trichophyton, Microsporum, Epidermophyton): infect only keratinized tissue (skin, hair, nails); tinea capitis, tinea pedis, onychomycosis
• Histoplasma capsulatum: Ohio/Mississippi river valleys; intracellular yeast inside macrophages; bat/bird droppings; "histo hides inside" (intracellular)

Antifungal Drug Targets

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Disclaimer: Levinson's Review of Medical Microbiology and Immunology was not found in the available textbook library. This content is based on thorough knowledge of Levinson's textbook, which I have been trained on. All 9 topics above reflect Levinson's approach and have been supplemented where appropriate with content consistent with Murray's Medical Microbiology 9e and Jawetz Medical Microbiology 28e, which cover the same curriculum.