3.1 Medical Microbiology

Medical microbiology examines the bacteria, viruses, fungi, and parasites that cause human disease and the antimicrobial agents used to treat them. For the FPGEE, you need a working knowledge of microbial structure, classification, pathogenesis, and resistance — Domain 1 of the NABP Content Outline pairs these concepts with immunology and pathophysiology to form the foundational biomedical sciences.

Bacterial Structure and Classification

Bacteria are prokaryotes that lack a nucleus. The gram stain divides them into two large groups based on cell-wall composition. Gram-positive organisms retain crystal violet and appear purple because they have a thick peptidoglycan layer (20 to 80 nm) with teichoic acids woven through it. Gram-negative organisms lose the stain and appear pink; they have a thin peptidoglycan layer (2 to 7 nm) surrounded by an outer membrane containing lipopolysaccharide (LPS), an endotoxin that triggers fever and septic shock when released during bacterial death.

Common shapes are cocci (spheres), bacilli (rods), and spirochetes (spirals). Atypical bacteria include Mycoplasma (no cell wall, unaffected by beta-lactams) and Chlamydia and Rickettsia (obligate intracellular pathogens).

Viruses

Viruses are acellular entities consisting of nucleic acid (DNA or RNA) wrapped in a protein capsid; some add a lipid envelope derived from host membranes. Replication follows the stages of attachment, penetration, uncoating, biosynthesis, assembly, and release. Lytic cycles destroy the host cell; lysogenic cycles integrate viral DNA into the host genome. In human disease, latency allows viruses such as herpes simplex (HSV), varicella-zoster (VZV), and HIV to persist in dormant form and reactivate later. Oncogenic viruses (HPV, EBV, HBV, HTLV-1) drive malignant transformation through oncogene expression or tumor-suppressor inhibition.

Fungi

Fungi are eukaryotes. Yeasts are single-celled; molds grow as branching hyphae. Dimorphic fungi switch forms depending on temperature — Histoplasma, Blastomyces, and Coccidioides grow as molds in the environment at 25 degrees C and as yeasts in tissue at 37 degrees C. Opportunistic mycoses such as Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause disease when host immunity falters. Fungal cell walls contain ergosterol, the target of polyene antifungals (amphotericin B) and azole antifungals (fluconazole, voriconazole).

Parasites

Protozoa are single-celled eukaryotes (Plasmodium, Giardia, Toxoplasma, Trichomonas). Helminths are multicellular worms grouped as nematodes, cestodes, and trematodes. Ectoparasites such as lice and scabies mites live on the skin. Antiparasitic therapy targets unique features: aminoquinolines block heme polymerization in malaria; benzimidazoles disrupt helminth microtubules; ivermectin opens parasite glutamate-gated chloride channels.

Normal Flora and Opportunistic Infection

The skin, gut, vagina, and respiratory tract host resident normal flora that compete with pathogens and prime the immune system. Disruption by antibiotics, catheters, or immunosuppression lets opportunists such as Candida, Clostridioides difficile, and coagulase-negative staphylococci overgrow. C. difficile is the classic antibiotic-associated colitis pathogen, releasing toxins A and B that cause pseudomembranous colitis.

Antimicrobial Targets and Resistance

Antibiotics exploit selective toxicity against bacterial structures absent from human cells:

• Cell wall synthesis — beta-lactams (penicillins, cephalosporins, carbapenems) bind penicillin-binding proteins; vancomycin binds D-Ala-D-Ala.
• Protein synthesis — aminoglycosides and tetracyclines act at the 30S subunit; chloramphenicol, macrolides, and clindamycin act at the 50S subunit.
• DNA and RNA synthesis — fluoroquinolones inhibit DNA gyrase and topoisomerase IV; rifampin inhibits bacterial RNA polymerase.
• Folate metabolism — sulfonamides and trimethoprim block sequential steps in tetrahydrofolate synthesis.
• Cell membrane — polymyxins (colistin) disrupt the gram-negative outer membrane.

Resistance mechanisms include beta-lactamases (which hydrolyze the beta-lactam ring; extended-spectrum beta-lactamases and carbapenemases extend the spectrum), altered targets (MRSA's PBP2a; mutated ribosomes), efflux pumps (tetracycline and fluoroquinolone export), reduced permeability through porin loss, and biofilm formation (protected communities on catheters and heart valves). Horizontal gene transfer via plasmids, transposons, and bacteriophages spreads resistance between organisms and across species.

Key Pathogens by Body System

• Respiratory: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, plus respiratory viruses.
• Gastrointestinal: Escherichia coli (ETEC, EHEC), Salmonella, Shigella, Campylobacter, C. difficile.
• Urinary tract: E. coli (most common), Klebsiella, Proteus, Enterococcus.
• Skin and soft tissue: Staphylococcus aureus (including MRSA), Streptococcus pyogenes.
• Bacteremia and sepsis: S. aureus, E. coli, Klebsiella, Pseudomonas aeruginosa.

flowchart LR
    A[Bacterial Cell] --> B[Peptidoglycan<br/>beta-lactams, vancomycin]
    A --> C[30S Ribosome<br/>aminoglycosides, tetracyclines]
    A --> D[50S Ribosome<br/>macrolides, clindamycin]
    A --> E[DNA Gyrase<br/>fluoroquinolones]
    A --> F[Folate Pathway<br/>sulfonamides, trimethoprim]
    A --> G[Outer Membrane<br/>polymyxins]