📘 Complete Medical Microbiology · USMLE

Genetic transfer

• Transformation: uptake of free DNA (competent: S. pneumoniae, H. influenzae, Neisseria).
• Conjugation: F⁺×F⁻ (plasmid transfer), Hfr×F⁻ (chromosomal gene transfer).
• Transduction: generalized (any gene) vs. specialized (adjacent genes). Lysogenic conversion: diphtheria, cholera, Shiga, botulinum toxins.

Growth & virulence

• Growth phases: lag, log (antibiotics most effective), stationary, death.
• Virulence factors: capsules (anti‑phagocytic), M protein, IgA protease, type III secretion.
• Intracellular pathogens: M. tuberculosis, Listeria, Salmonella, Legionella.

Bacterial toxins

• Endotoxin (LPS): lipid A, TLR4, TNF‑α, shock.
• Exotoxins: A‑B toxins, superantigens (TSST‑1), neurotoxins (tetanus, botulinum), enterotoxins (cholera, heat‑stable).
• Notable: diphtheria toxin (ADP‑ribosylates eEF‑2), Shiga toxin (60S ribosome), exotoxin A (Pseudomonas).

Staphylococcus

• S. aureus: coagulase+, β‑hemolytic, protein A, TSST‑1, enterotoxins. Diseases: abscess, osteomyelitis, endocarditis, toxic shock, scalded skin, food poisoning.
• S. epidermidis: coagulase‑, novobiocin S, biofilm → catheter infections, prosthetic valve endocarditis.
• S. saprophyticus: novobiocin R → UTI in young women.

Streptococcus

• Group A (S. pyogenes): β‑hemolytic, bacitracin S, M protein. Pharyngitis, scarlet fever, rheumatic fever, glomerulonephritis, necrotizing fasciitis.
• Group B (S. agalactiae): β‑hemolytic, CAMP+, hippurate+. Neonatal sepsis/meningitis; intrapartum prophylaxis.
• S. pneumoniae: α‑hemolytic, optochin S, bile soluble. Pneumonia, meningitis, otitis. PCV13/PPSV23 vaccines.
• Viridans: α‑hemolytic, optochin R. Dental caries, subacute endocarditis (S. mutans, S. sanguinis, S. gallolyticus).

Gram‑positive rods (spore‑formers & others)

• Listeria monocytogenes: tumbling motility, intracellular, cold enrichment. Ampicillin + gentamicin. Neonatal meningitis, pregnancy.
• Corynebacterium diphtheriae: club‑shaped, metachromatic granules, β‑prophage toxin (ADP‑ribosylates eEF‑2). Pseudomembrane, myocarditis. Antitoxin + erythromycin.
• Bacillus anthracis: capsule (poly‑D‑glutamate), anthrax toxin (PA, LF, EF). Cutaneous/pulmonary. Ciprofloxacin or doxycycline.
• Bacillus cereus: emetic (rice, 1‑6h) and diarrheal (8‑18h) food poisoning.
• Clostridium tetani: tetanospasmin (blocks GABA/glycine) → spastic paralysis. TIG + metronidazole.
• Clostridium botulinum: toxin blocks ACh release → flaccid paralysis. Antitoxin, supportive.
• Clostridium perfringens: gas gangrene (α‑toxin, lecithinase), food poisoning (enterotoxin). Penicillin + debridement.
• Clostridioides difficile: toxin A/B → pseudomembranous colitis. Vancomycin or metronidazole; fecal transplant.
• Actinomyces israelii: anaerobic, sulfur granules, lumpy jaw. Penicillin G.
• Nocardia: aerobic, partially acid‑fast, brain abscess. TMP‑SMX.

Enterobacteriaceae

• E. coli: UTI, neonatal meningitis (K1), traveler’s diarrhea (ETEC), EPEC, EIEC, EAEC, EHEC O157:H7 (Shiga‑like, HUS – avoid antibiotics).
• Klebsiella pneumoniae: pneumonia (currant‑jelly sputum), ESBL/KPC. Klebsiella granulomatis (Donovanosis) – doxycycline.
• Shigella: non‑motile, low ID, Shiga toxin (S. dysenteriae), dysentery. Azithromycin/ciprofloxacin.
• Salmonella: Typhi (Vi capsule, typhoid fever, rose spots), non‑typhi (gastroenteritis, osteomyelitis in sickle cell). Fluoroquinolones or ceftriaxone.
• Yersinia: pestis (plague, bipolar staining, aminoglycosides), enterocolitica (pseudoappendicitis).
• Proteus: urease+, swarming motility, staghorn calculi. Fluoroquinolones/TMP‑SMX.

Non‑enteric Gram‑negative

• Pseudomonas aeruginosa: oxidase+, pyocyanin, biofilm, exotoxin A. Burns, CF, UTI, otitis externa, ecthyma gangrenosum. Anti‑pseudomonal β‑lactam + aminoglycoside.
• Legionella pneumophila: BCYE, intracellular, hyponatremia, diarrhea. Azithromycin/levofloxacin.
• Bordetella pertussis: pertussis toxin (ADP‑ribosylates Gi), catarrhal → paroxysmal → convalescent. Macrolide.
• Haemophilus influenzae: type b (PRP capsule), X/V factors, satellite growth. Meningitis, epiglottitis, pneumonia. Ceftriaxone.
• Neisseria: meningitidis (maltose+, capsule, complement deficiency), gonorrhoeae (glucose+, no vaccine). Ceftriaxone + azithromycin.
• Moraxella catarrhalis: otitis media, COPD exacerbations. Amoxicillin‑clavulanate.
• Campylobacter jejuni: curved, microaerophilic, bloody diarrhea, Guillain‑Barré. Macrolide if severe.
• Helicobacter pylori: urease+, chronic gastritis, MALT lymphoma, gastric cancer. Triple/quadruple therapy.

Zoonotic & fastidious

• Brucella: undulant fever, doxycycline + rifampin.
• Francisella tularensis: rabbit/tick, ulceroglandular, pneumonic. Streptomycin/gentamicin.
• Pasteurella multocida: animal bites, amoxicillin‑clavulanate.
• Bartonella henselae: cat scratch disease (stellate granulomas), azithromycin.
• HACEK: oral flora, subacute endocarditis. Ceftriaxone.
• Vibrio cholerae: rice‑water diarrhea, cholera toxin (↑cAMP). Fluid replacement, doxycycline.
• Vibrio vulnificus: seafood, liver disease, necrotizing fasciitis. Doxycycline + ceftazidime.
• Gardnerella vaginalis: bacterial vaginosis (clue cells, whiff test). Metronidazole.
• Bacteroides fragilis: abdominal abscess, metronidazole.

Treponema pallidum (syphilis)

• Primary: painless chancre; secondary: maculopapular rash (palms/soles), condylomata lata; tertiary: gummas, aortitis, CNS (tabes dorsalis, general paresis).
• Diagnosis: nontreponemal (VDRL/RPR), treponemal (FTA‑ABS). Treatment: benzathine penicillin G; Jarisch‑Herxheimer reaction.

Borrelia burgdorferi (Lyme)

• Ixodes tick, erythema migrans (bull's‑eye), flu‑like, neurologic (Bell's palsy), cardiac (AV block), arthritis (immune‑mediated).
• Diagnosis: ELISA + Western blot. Doxycycline, amoxicillin, ceftriaxone for disseminated.

Leptospira interrogans

• Zoonotic (animal urine), Weil disease (hepatorenal failure, jaundice). Penicillin/doxycycline.

Chlamydia, Rickettsia, Mycoplasma

• Chlamydia trachomatis: D‑K (NGU, PID, inclusion conjunctivitis), L1‑3 (LGV), A‑C (trachoma). Azithromycin/doxycycline.
• Chlamydophila pneumoniae: atypical pneumonia (walking pneumonia), hoarseness.
• Chlamydophila psittaci: psittacosis (parrots), atypical pneumonia + hepatitis.
• Rickettsia rickettsii: RMSF (centripetal rash, palms/soles), vasculitis. Doxycycline.
• Ehrlichia/Anaplasma: fever, leukopenia, thrombocytopenia, morulae. Doxycycline.
• Coxiella burnetii: Q fever (aerosol, spore‑like), atypical pneumonia, hepatitis, endocarditis. Doxycycline.
• Mycoplasma pneumoniae: no cell wall, P1 adhesin, cold agglutinins, fried‑egg colonies. Macrolide or tetracycline.
• Ureaplasma urealyticum: urethritis, urease+. Erythromycin/tetracycline.

Mycobacterium tuberculosis

• Acid‑fast, aerobic, slow‑growing (Lowenstein‑Jensen), cord factor, sulfatides. Primary: Ghon focus → Ghon complex. Reactivation: upper lobe cavitary, hemoptysis.
• Diagnosis: AFB smear, culture, Quantiferon‑TB (IGRA), PPD (≥5 mm HIV+, ≥10 mm high‑risk, ≥15 mm low‑risk).
• Treatment: RIPE (rifampin, INH, pyrazinamide, ethambutol) for 2 months, then rifampin + INH for 4 months. MDR: bedaquiline, linezolid, fluoroquinolones.

Non‑tuberculous mycobacteria (MOTT)

• MAC: disseminated in AIDS (CD4 <50), pulmonary. Macrolide + ethambutol.
• M. kansasii: pulmonary (chronic lung). Rifampin + ethambutol + INH.
• M. marinum: fish‑tank granuloma. Minocycline/clarithromycin.
• M. ulcerans: Buruli ulcer. Rifampin + streptomycin.
• M. leprae: tuberculoid vs. lepromatous, cannot be cultured. Dapsone + rifampin; add clofazimine for lepromatous.

Systemic (endemic) mycoses

• Histoplasma capsulatum: Ohio/Mississippi, bird/bat droppings. Intracellular yeast (narrow‑neck budding). “Fungus flu”, hepatosplenomegaly, calcified lesions. Itraconazole or amphotericin B.
• Coccidioides immitis: Southwestern US (San Joaquin Valley). Arthroconidia → spherules + endospores. Valley fever, erythema nodosum. Itraconazole/fluconazole; amphotericin B for severe.
• Blastomyces dermatitidis: Great Lakes, SE US, rotting wood. Broad‑based budding yeast, double‑contoured wall. Itraconazole or amphotericin B.
• Paracoccidioides brasiliensis: South/Central America. Multiple buds (pilot wheel). Itraconazole.
• Sporothrix schenckii: rose gardeners, lymphocutaneous (cigar‑shaped yeast). Itraconazole.

Opportunistic fungi

• Candida albicans: germ tube+, pseudohyphae, true hyphae. Thrush, esophagitis, vaginitis, perleche, septicemia with endophthalmitis. Fluconazole, nystatin, amphotericin B.
• Aspergillus fumigatus: septate, dichotomous branching (45°). ABPA, aspergilloma, invasive (neutropenia, CGD). Voriconazole (invasive), itraconazole (ABPA).
• Cryptococcus neoformans: encapsulated yeast, pigeon droppings. Meningitis (HIV, Hodgkin), pulmonary. India ink (insensitive), antigen detection (CSF). Amphotericin B + flucytosine, then fluconazole.
• Mucorales (Rhizopus, Mucor, Absidia): non‑septate, broad, right‑angle branching. Rhinocerebral (DKA), neutropenia. Debridement + amphotericin B.
• Pneumocystis jirovecii: fungus (silver stain), extracellular. Pneumonia in AIDS (CD4 <200), ground‑glass infiltrates. TMP‑SMX (first‑line), dapsone.
• Malassezia furfur: pityriasis versicolor (spaghetti & meatballs), topical selenium or azoles.
• Dermatophytes: Trichophyton, Microsporum, Epidermophyton. Tinea infections. Topical azoles, oral griseofulvin/terbinafine for nails/hair.

Antifungal drugs

• Azoles: inhibit ergosterol synthesis (fluconazole, itraconazole, voriconazole). Hepatotoxicity, CYP interactions.
• Polyenes: amphotericin B (binds ergosterol, pores). Nephrotoxicity.
• Echinocandins: inhibit β‑glucan synthase (caspofungin, micafungin). Well tolerated.
• Flucytosine: inhibits DNA/RNA synthesis. Myelosuppression.

Protozoa

• Entamoeba histolytica: flask‑shaped colonic ulcers, liver abscess (trophozoites with central karyosome). Metronidazole + paromomycin.
• Giardia lamblia: falling‑leaf motility, bilobed nuclei, foul‑smelling fatty diarrhea. Metronidazole.
• Cryptosporidium: acid‑fast oocysts, severe in AIDS. Nitazoxanide.
• Cystoisospora belli: elliptical oocysts, TMP‑SMX.
• Cyclospora: spherical acid‑fast oocysts, UV fluorescence, TMP‑SMX.
• Microsporidia: spores in stool; no proven treatment.
• Trichomonas vaginalis: frothy discharge, strawberry cervix, corkscrew motility. Metronidazole.
• Plasmodium: vivax/ovale (hypnozoites, primaquine), malariae (72h quartan), falciparum (cerebral, artemether‑lumefantrine), knowlesi (24h).
• Trypanosoma cruzi: Chagas (kissing bug), Romaña sign, dilated cardiomyopathy. Benznidazole.
• Trypanosoma brucei: African sleeping sickness (tsetse), antigenic variation. Suramin (acute), melarsoprol (CNS).
• Leishmania: visceral (L. donovani), mucocutaneous (L. braziliensis). Sandfly, amastigotes in macrophages. Stibogluconate.
• Babesia microti: Ixodes tick, malaria‑like, Maltese cross. Clindamycin + quinine.
• Toxoplasma gondii: cat, congenital (hydrocephaly, calcifications, chorioretinitis), ring‑enhancing brain lesions in AIDS. Pyrimethamine + sulfadiazine.
• Naegleria fowleri: PAM (warm freshwater), amphotericin B.
• Acanthamoeba: keratitis (contact lens), granulomatous encephalitis. Miconazole, propamidine.

Helminths (metazoa)

• Nematodes: Enterobius (pinworm – tape prep), Trichuris (whipworm), Ascaris (lung migration), Toxocara (visceral larva migrans), hookworm (anemia), Strongyloides (autoinfection), Trichinella (encysted in muscle), Wuchereria/Brugia (elephantiasis), Onchocerca (river blindness, skin snips), Dracunculus (guinea worm).
• Trematodes: Schistosoma (mansoni, japonicum, haematobium – bladder cancer), Clonorchis (liver fluke), Fasciola (watercress), Paragonimus (lung fluke, hemoptysis). Praziquantel (except Fasciola – triclabendazole).
• Cestodes: Taenia saginata (beef), Taenia solium (pork – cysticercosis), Diphyllobothrium latum (fish – B12 deficiency), Echinococcus (hydatid cysts). Praziquantel (surgery for Echinococcus).

DNA viruses

• Herpesviridae: HSV‑1 (oral, keratitis, encephalitis – temporal lobe), HSV‑2 (genital, neonatal). Acyclovir (requires TK). VZV (chickenpox, shingles). EBV (mononucleosis, heterophile+, Downey cells, Burkitt, NPC). CMV (owl‑eye, heterophile‑negative, retinitis, congenital). HHV‑6 (roseola), HHV‑8 (Kaposi sarcoma).
• HPV: 6,11 (warts), 16,18 (cancer). E6/E7 inactivate p53/Rb. Gardasil‑9.
• Parvovirus B19: slapped‑cheek, aplastic crisis (sickle cell), hydrops fetalis.
• Poxviridae: variola (smallpox – Guarnieri bodies), molluscum contagiosum (umbilicated).
• Hepadnaviridae: HBV (partially dsDNA, chronic, HCC). HBsAg, anti‑HBc IgM, HBeAg.
• Adenoviridae: ARD, conjunctivitis, gastroenteritis.
• Polyomaviridae: JC (PML), BK (nephropathy).

RNA viruses

• Picornaviridae: polio (flaccid paralysis), Coxsackie A (HFMD, herpangina), Coxsackie B (pleurodynia, myocarditis), echovirus (rash, meningitis), rhinovirus (common cold), HAV (acute hepatitis).
• Caliciviridae: norovirus (gastroenteritis, cruise ships).
• Hepeviridae: HEV (enteric, severe in pregnancy).
• Flaviviridae: HCV (chronic, HCC), yellow fever, dengue (breakbone, hemorrhagic), Zika (microcephaly), West Nile (encephalitis), St. Louis encephalitis.
• Togaviridae: rubella (congenital – cataracts, PDA, deafness), chikungunya (arthralgia), EEE/WEE/VEE (encephalitis).
• Coronaviridae: SARS‑CoV‑2 (ACE2, anosmia, mRNA vaccines), MERS, SARS.
• Retroviridae: HIV (CD4 depletion, CCR5/CXCR4, HAART). Gag (p24), Pol (RT, integrase, protease), Env (gp120/gp41).
• Paramyxoviridae: measles (3 Cs, Koplik, SSPE), mumps (parotitis, orchitis), parainfluenza (croup), RSV (bronchiolitis, palivizumab), metapneumovirus.
• Orthomyxoviridae: influenza (drift/shift, neuraminidase inhibitors, vaccines).
• Rhabdoviridae: rabies (Negri bodies, hydrophobia, hRIG + vaccine).
• Filoviridae: Ebola (contact, high mortality, rVSV‑ZEBOV).
• Bunyaviridae: hantavirus (pulmonary syndrome), California/La Crosse encephalitis.
• Arenaviridae: LCMV, Lassa (ribavirin).
• Reoviridae: rotavirus (infant gastroenteritis – oral vaccine), Colorado tick fever.

Prions & slow viruses

• Prion diseases: CJD (sporadic, genetic, variant – vCJD from BSE), kuru (cannibalism), GSS, fatal familial insomnia. Spongiform encephalopathy, 14‑3‑3 protein, vacuolation.
• Slow conventional viruses: SSPE (measles), HIV dementia, PML (JC virus).

Skin & soft tissue

• Impetigo (S. pyogenes / S. aureus), cellulitis, erysipelas (S. pyogenes), necrotizing fasciitis (Group A, mixed).
• Furuncles, carbuncles (S. aureus), hot tub folliculitis (Pseudomonas).
• Cat scratch (Bartonella), fish‑tank granuloma (M. marinum), sporotrichosis (Sporothrix).
• Malignant pustule (B. anthracis), ecthyma gangrenosum (Pseudomonas).
• Animal bites: Pasteurella (dog/cat), Eikenella (human), Capnocytophaga (dog, asplenic).

Respiratory

• Typical pneumonia: S. pneumoniae (rusty sputum), Klebsiella (currant‑jelly), Pseudomonas (CF, neutropenia), S. aureus (post‑influenza).
• Atypical: Mycoplasma (young adults), Legionella (hyponatremia), Chlamydophila, Pneumocystis (CD4 <200).
• TB, endemic fungi (Histoplasma, Coccidioides, Blastomyces). Pertussis (whoop), croup (parainfluenza), RSV (bronchiolitis).

GI & hepatobiliary

• Diarrhea: viral (rotavirus, norovirus), bacterial (Salmonella, Shigella, Campylobacter, Yersinia, C. difficile, ETEC, EIEC, EHEC).
• Hepatitis A‑E: HAV/HEV (enteric, no chronic), HBV/HCV (parenteral, chronic, HCC). HDV requires HBV.
• Peritonitis (mixed anaerobes + facultatives), liver abscess (Entamoeba, Echinococcus).
• Pancreatitis (mumps).

CNS

• Meningitis: neonates (GBS, E. coli, Listeria), children (H. influenzae, N. meningitidis), elderly (S. pneumoniae).
• Encephalitis: HSV‑1 (temporal lobe, RBCs in CSF), arboviruses (WNV, EEE), rabies.
• Brain abscess (mixed streptococci + Bacteroides), neurocysticercosis (Taenia solium).
• CSF: bacterial (PMN, low glucose, high protein), viral (lymphocytes, normal glucose).

GU & STI

• Urethritis: N. gonorrhoeae (PMN diplococci), C. trachomatis, Ureaplasma, Trichomonas.
• Cystitis: E. coli (#1), S. saprophyticus (young women). Pyelonephritis: E. coli, Staphylococcus.
• Genital lesions: HSV (painful vesicles), syphilis (indurated painless), chancroid (H. ducreyi – painful), LGV (C. trachomatis), granuloma inguinale (Klebsiella).
• PID: N. gonorrhoeae, C. trachomatis (post‑menses).
• Vaginal discharge: bacterial vaginosis (clue cells, fishy), Candida (cottage cheese), Trichomonas (motile).

Cardiac & hematologic

• Endocarditis: acute (S. aureus), subacute (viridans, HACEK, enterococci).
• Myocarditis (Coxsackie B, T. cruzi).
• Mononucleosis (EBV – heterophile+, Downey cells), malaria (rings/schizonts), babesiosis (multiple rings), leishmaniasis.
• Megaloblastic anemia (Diphyllobothrium), microcytic anemia (hookworm, Trichuris).
• Lymphocytosis with cough (Bordetella pertussis).

Bone & joint

• Osteomyelitis: #1 S. aureus; neonates (GBS, Gram‑neg); sickle cell (Salmonella); trauma (Pseudomonas).
• Septic arthritis: S. aureus (all ages); 15‑40 (N. gonorrhoeae).
• Prosthetic joint: coagulase‑negative staphylococci.
• Reactive arthritis: post‑enteric (Salmonella, Shigella, Campylobacter, Yersinia) or post‑chlamydial.
• Lyme arthritis (B. burgdorferi).