• Catalase catalyzes:

• Myeloperoxidase catalyzes:

• Sites of action of antimicrobial agents include cell wall synthesis, cell-membrane integrity, DNA replication, protein synthesis, DNA-dependent RNA polymerase, and folic acid metabolism.

VIROLOGY

• Virology terminology: virion, capsid, capsomere, nucleocapsid, and genome.

• Viral genomes:

• DNA viruses:

   • Herpesviruses, hepadnaviruses, poxviruses, adenoviruses, papillomaviruses, polyomaviruses, and parvoviruses.

   • All DNA viruses are double-stranded (ds), except parvoviruses (ss).

   • All DNA viruses have linear DNA, except papillomaviruses and polyomaviruses (ds, circular) and hepadnaviruses (incomplete ds, circular).

• RNA viruses:

   • (+)ssRNA (same as mRNA) viruses: picornaviruses, caliciviruses, flaviviruses, togaviruses, hepeviruses, astroviruses, and coronaviruses.

   • Retroviruses contain two strands of (+)ssRNA that is NOT mRNA (diploid).

   • (–)ssRNA viruses: orthomyxoviruses, paramyxoviruses, rhabdoviruses, bunyaviruses, arenaviruses, filoviruses, hepatitis D virus; require viral RNA polymerase within the virions.

   • dsRNA viruses: reoviruses; require viral RNA polymerase within the virions.

   • Segmented RNA viruses: orthomyxoviruses, reoviruses, bunyaviruses, and arenaviruses.

• Viral replication:

• Obligate intracellular parasites, use viral attachment proteins to attach to host cell receptors.

• Growth cycle: attachment, entry, uncoating, macromolecular synthesis, assembly, and release.

• Viral disease patterns: acute, chronic, persistent (virions produced), and latent (no virions produced).

• DNA viruses replicate in the host nucleus EXCEPT poxviruses.

• RNA viruses replicate in the host cytoplasm EXCEPT influenza viruses.

• Viruses that use reverse transcriptase (RT) have cytoplasmic and nuclear replication phases:

   • Retroviruses: vRNA–RT → vDNA in cytoplasm; vDNA integrates into host chromosome; host RNA polymerase (RNAP) produces vRNA in nucleus.

   • Hepadnaviruses: vDNA to nucleus; host RNAP produces vRNA genome template; vRNA–RT → vDNA in cytoplasm.

Hepatitis Viruses

• Hepatitis A virus (HAV): Picornavirus; (+)ssRNA; fecal–oral transmission, no chronic carriers; killed virus vaccine.

• Hepatitis B virus (HBV): Hepadnavirus; partially complete circular dsDNA; parental, sexual, vertical (intrapartum, postpartum) transmission; acute and chronic disease; hepatocellular carcinoma; and recombinant HBsAg vaccine.

• Hepatitis C virus (HCV): Flavivirus; (+)ssRNA; parental or sexual transmission; acute and chronic disease; and hepatocellular carcinoma.

• Hepatitis D virus (HDV): Delta virus; (-)ssRNA; defective virus, requires HBV coinfection; acute and chronic infections.

• Hepatitis E virus (HEV): Hepevirus; (+)ssRNA; fecal–oral transmission; no chronic carriers; high mortality in pregnant women.

DNA Viruses

• Parvovirus B19: ssDNA; causes fifth disease/erythema infectiosum (slapped cheek appearance).

• Papillomavirus (HPV): circular dsDNA; causes common warts, HVP types 1, 4; condyloma accuminatum, HPV 6, 11; cervical and other genital carcinomas, HPV 16, 18; recombinant vaccines for HPV 6/11/16/18 and HPV 16/18.

• Polyomaviruses: circular dsDNA; BK virus, hemorrhagic cystitis; JC virus, progressive multifocal leukoencepalopathy; disease occurs only in immunocompromised.

• Adenoviruses: dsDNA; pharyngoconjunctivitis in children, ARDS in young adults (especially military), and gastroenteritis (serotypes 40/41).

• Herpesviruses: dsDNA; latent infections occur with all; reactivation infections occur with immunocompromisation.

• Herpes simplex virus type 1: primarily oral; latent in neurons, especially trigeminal ganglia; cold sores, keratitis, sporadic encephalitis (temporal lobe); and acyclovir.

• HSV 2: primarily genital; latent in neurons, especially sacral ganglia; herpes genitalis; neonatal disease; sexually transmitted; and acyclovir.

• Varicella-zoster virus (VZV): latent in neurons; primary infection, chickenpox, lesions occur in crops; reactivation infection, shingles, lesions occur in dermatomal distribution; acyclovir, valacyclovir; and live attenuated virus vaccine.

• Cytomegalovirus (CMV): ubiquitous; direct contact, sexual, vertical transmission; causes retinitis and pneumonitis in immunocompromised; neonates suffer from CMV inclusion disease; ganciclovir, and foscarnet.

• Epstein–Barr virus (EBV): infects B lymphocytes; infectious mononucleosis, positive for heterophile antibodies (monospot test); specific EBV antigens also used to diagnose infection—early antigen (EA), viral capsid antigen (VCA), Epstein–Barr nuclear antigen (EBNA).

• HHV6: roseola infantum.

• HHV8: Kaposi sarcoma in AIDS.

• Poxviruses: largest, most complex viruses, and dsDNA.

• Variola virus: smallpox, extinct since 1977; potential bioterrorism agent.

• Vaccinia virus: vaccine strain against smallpox; can cause infection especially in immunocompromised.

• Molluscipoxvirus: molluscum contagiosum; pearly nodular lesions.

Positive ssRNA Viruses

• Picornaviruses (+ssRNA): polioviruses, coxsackieviruses A and B, echo-viruses, enteroviruses, HAV, and rhinoviruses.

• All enteroviruses multiply in upper respiratory and gastrointestinal tracts; mild upper respiratory infections (URI), rashes, aseptic meningitis (lymphocytic pleocytosis, normal glucose, and normal/slightly elevated protein).

• Poliovirus: paralytic poliomyelitis; eradicated in the United States; two vaccines, Salk inactivated and Sabin live attenuated vaccines; US now uses killed vaccine only.

• Coxsackievirus A: herpangina, hand-foot-and-mouth disease.

• Coxsackievirus B: myocarditis.

• Rhinoviruses: multiply only in URT; common cold.

• Flaviviruses: all arthropod-borne EXCEPT HCV.

• Encephalitis (meningitis): West Nile virus, St. Louis encephalitis virus.

• Fever with rash, hemorrhagic fever: dengue viruses, yellow fever viruses.

• Togaviruses: all arthropod-borne EXCEPT rubella virus

• Encephalitis: alphaviruses—Eastern equine encephalitis virus, Western equine encephalitis virus, and Venezuelan equine encephalitis virus.

• Rubella virus: rubella or German measles; causes severe birth defects; live attenuated vaccine.

• Coronaviruses: most strains cause common cold; also severe acute respiratory syndrome (SARS).

• Retroviruses:

• HIV-1: diploid genome, gag, env, pol genes; major proteins, p24 (diagnosis), gp120 and gp 41 attachment, reverse transcriptase (RT), integrase (IN), protease (PR); RT, IN, PR targets for antiretroviral therapy; acute retroviral syndrome, AIDS (CD4 T-cell count <200/µL), and/or AIDS-defining opportunistic infections (Cryptosporidium, Pneumocystis, Mycobacterium avium-intracellular, many others), cancers (Kaposi sarcoma, others), dementia, or wasting.

• HTLV-1: acute T-cell leukemia/lymphoma; tropical spastic paraparesis.

Negative ssRNA Viruses

• Require virion-associated RNA-dependent RNA polymerase.

• Paramyxoviruses:

• Measles virus: measles (rubeola or hard measles)—cough, coryza, conjunctivitis, photophobia, Koplik spots; maculopapular rash; pneumonia, encephalitis; SSPE; and live attenuated vaccine.

• Mumps virus: mumps (swelling of salivary, parotid glands); aseptic meningitis, orchitis; and live attenuated vaccine.

• Respiratory syncytial virus: bronchiolitis and pneumonia in infants; ribavirin, palivizumab.

• Parainfluenza viruses: croup.

• Rhabdovirus: (rabies virus): bullet-shaped appearance; causes rabies; skunks, raccoons, foxes, coyotes/dogs, and bats are main reservoirs in the United States; animal bite transmission through saliva; control animal vectors; Negri body—eosinophilic intracytoplasmic inclusion body in infected cells (brain, nuchal skin, and cornea).

• Orthomyxoviruses: Influenza viruses A and B; segmented genomes; genetic drift, minor antigen changes IA, IB; genetic shift, major antigen change to new hemagglutinin (H) and/or neuraminidase (N), IA only; oseltamivir, zanamivir for treatment; previously amantidine, rimantidine but most circulating strains resistant.

• Bunyaviruses: La Crosse virus, California encephalitis virus; hantaviruses.

• Arenaviruses: lymphocytic choriomeningitis virus; viruses that cause hemorrhagic fever (Lassa virus, Tacaribe virus).

dsRNA Viruses: Double-Shelled Capsids

• Rotaviruses: cause infantile diarrhea, live attenuated vaccine.

• Coltivirus: Colorado tick fever.

BACTERIOLOGY

• Gram-positive cocci: staphylococci catalase +, streptococci catalase -.

• Staphylococcus aureus: Mannitol-salt agar (selective and differential), yellow colonies, coagulase +, mannitol +, catalase +; some are methicillin resistant (MRSA), some have vancomycin resistance emerging (VISA); protein A binds IgG Fc inhibiting phagocytosis, causes rapid-onset food poisoning (preformed enterotoxin), toxic shock syndrome, scalded skin syndrome, osteomyelitis, acute bacterial endocarditis (IV drug users), abscesses, and recurrent infection in chronic granulomatous disease (CGD).

• Staphylococcus saprophyticus: second leading cause of urinary tract infection (UTI) in young sexually active females.

• Streptococci: β-hemolytic divided into groups (13 groups: A-O) based on cell wall carbohydrate antigens. Group A divided into >50 types based on M proteins (virulence, specific immunity), catalase negative.

• Streptococcus pyogenes (group A): hyaluronic acid capsule, carbohydrate antigen, M protein, bacitracin sensitive, cellulitis, rheumatic fever, glomerulonephritis, necrotizing fasciitis, erysipelas, and scarlet fever.

• Viridans: include S. mitis, and so on. Normal oral flora, α-hemolytic, subacute bacterial endocarditis after dental/oral surgery.

• Enterococcus (used to be called Streptococcus) faecalis (group D): normal intestinal flora, subacute bacterial endocarditis after pelvic/abdominal surgery, UTIs, growth in 6.5% NaCl.

• Streptococcus agalactiae (group B): sometimes normal vaginal flora; in dairy products (cattle pathogen); neonatal sepsis; (CAMP) test +.

• Peptostreptococci: normal oral/vaginal flora, endocarditis, and lung abscess.

• Streptococcus pneumoniae: pneumonia, meningitis, otitis media (children), optochin sensitive, bile soluble, use Quellung reaction (capsule Ags, host Abs), and pneumococcal polyvalent vaccine.

• Dick test: test susceptibility to scarlet fever.

• Schultz-Charlton test: determine if rash is due to erythrogenic toxin of scarlet fever.

• Gram-negative cocci (Neisseria): oxidase +, diplococci, polysaccharide capsule, endotoxin, associated with C5, C6, V7, C8 complement deficiency; pathogenic forms: Thayer-Martin agar –, chocolate agar +, nutrient agar –, 37°C growth +, room temperature –; nonpathogenic forms: Thayer-Martin agar –, chocolate agar +, nutrient agar +, 37°C growth +, and room temperature +.

• Neisseria meningitidis: capsule, endotoxin, toxemia, petechiae, hemorrhage, disseminated intravascular coagulation (DIC), and Waterhouse–Friderichsen syndrome.

• Bacterial meningitis: in <40-year-old = S. pneumoniae; >40-year-old = S. pneumoniae; 2 to 6 months + neonates = Group B streptococci, Escherichia coli; and neonates to 5-year-old children = N. meningitidis.

• Neisseria gonorrhoeae: pili, endotoxin, IgA protease, pharyngitis, proctitis, pelvic inflammatory disease (PID), urethritis, and cervicitis.

• Gram-positive bacilli: aerobic (Bacillus); anaerobic (Clostridium), killed by autoclave. All are spore formers.

• Bacillus anthracis: polypeptide capsule, exotoxin, and anthrax (Woolsorters disease).

• Bacillus cereus: food poisoning (food reheated once), enterotoxin.

• Clostridium: no cytochrome enzymes, no catalase, and no superoxide dismutase.

• Clostridium tetani: noninvasive, neurotoxins (prevents release of neural inhibitory transmitters such as γ-aminobutyric acid [GABA] and glycine), lockjaw, spastic paralysis; give toxoid/antitoxin.

• Clostridium botulinum: noninvasive, exotoxins (prevents acetylcholine release), flaccid paralysis, and antitoxin (honey ingestion in infancy).

• Clostridium perfringens: invasive, enterotoxin, food poisoning, myonecrosis, collagenase, lecithinase, and gas gangrene.

• Clostridium difficile: Pseudomembranous colitis can occur after broad-spectrum antibiotic usage.

• Corynebacterium diphtheriae: Gram-positive rod, metachromatic granules, exotoxin (inhibits EF-2 and protein synthesis).

• Listeria monocytogenes: Gram-positive rod in cerebrospinal fluid (CSF), compromised host, neonate, diarrhea after eating raw cheeses, and tumbling motility.

• Salmonella: motile Gram-negative rod, enteric fever, food poisoning; Salmonella typhi = human pathogen; other species = animal pathogens; motile; and nonlactose fermenter.

• Shigella: nonmotile Gram-negative rod, more virulent than Salmonella, bloody diarrhea, shigellosis is human disease, oral–anal route (fingers, flies, food, and feces), toxin inhibits protein synthesis.

• Escherichia coli: Gram-negative rod, most common UTI, sepsis (serious); enterohemorrhagic E. coli (EHEC) (colitis, hemolytic uremic syndrome—verotoxin, hamburger, beef); enteroinvasive E. coli (EIEC) (fever, bloody stool, and diarrhea); enterotoxigenic E. coli (ETEC) (traveler diarrhea); enteropathogenic E. coli (EPEC) (infant fever and diarrhea, nonbloody stool).

• Pseudomonas aeruginosa: Gram-negative rod, antibiotic resistance, blue–green pigments; causes UTI, wounds, burns, greenish-yellow sputum.

• Klebsiella: Gram-negative, large capsule; causes UTI, pneumonia, especially in alcoholics (currant jelly sputum).

• Haemophilus influenzae: Gram-negative rod; causes meningitis, otitis, sinusitis, and epiglottitis.

• Proteus: Gram-negative rod, result in swarming growth; produce urease (urea →, NH₃); also produced by Helicobacter pylori and Ureaplasma urealyticum; causes UTI, wounds, renal stones, and large staghorn calculi.

• Gardnerella vaginalis: Gram-negative, “clue cells”; vaginitis with discharge (fishy smell, conduct Whiff test).

• Bordetella pertussis: Gram-negative, capsule form, pili, killed vaccine, causes whooping cough.

• Yersinia pestis: Gram-negative, “safety pin” (bipolar staining), causes plague (bubonic/pneumonic), spread by rat flea.

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