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Flashcards in Intracellular Bacteria Deck (25)

Major Intracellular Pathogens

-Cocci: Neisseria
-Enterics: Shigella, E. coli (EIEC), Salmonella, Yersinia
-Rickettsial: Rickettsia, Ehrlichia, Anaplasma and C. burnetti
-Listeria- accidental opportunistic
-Some Bacilli (B anthracis)
-Some systemic fungal infections: Histoplasma, Cryptococcus


Obligate vs Facultative Intracellular Parasites

-Obligate intracellular parasites can ONLY reproduce within host cells: must be provided with host cells to grow in vitro ( cell culture, tissue culture)
-Rickettsial, Chlamydia, Viruses

-Facultative intracellular parasites can replicate independently when they have the right nutrients: may be fastidious, but can grow on agar plate
-Enterics (closer to replicating on own)
-Bacilli (closer to replicating on own)
-Legionella (closer to obligate)


Recurring theme of bacterial intracellular pathogenesis- macrophages

-use of infected macrophages for transport to target site of infection
-enterics: typhoid fever
-Mycobacter: TB
-Fungi: Histoplasma


Recurring theme of bacterial intracellular pathogenesis- T3SS

-host cell takeover by Type 3 Secretion Systems
-enhance phagocytosis by target cell type
-alter endosome so that lysosomal fusion fails
-Enterics, Legionella, Mycobacter


Recurring theme of bacterial intracellular pathogenesis- Actin based motility

-virulence factors with names like "ActA"
-generate an actin "tail" behind bacteria free in the cytoplasm
-bacteria can eventually ram through cell membrane into next cell
-Listeria and Shigella


Recurring theme of bacterial intracellular pathogenesis- humoral immunity

-intracellular lifestyles evades humoral immune system
-enterics: use of M cells as gateway to exterior surface of intestine, works around colonization resistance and tight junctions on interior surface
-actin- based cell-cell spread allows infection of new cells without exposure to humoral immunity
-CMI required to clear infection (like viruses)


Recurring theme of bacterial intracellular pathogenesis- effective antibiotics

-effective antibiotic treatment for bacteria that are primarily intracellular in the body requires drugs that can penetrate the host cell membrane (not just circulate in the blood)
-Rickettsial, Legionella, Chlamydia
-Tetracyclines are the first choice
-Contraindicated in pregnancy
-Alternates: azithromycin, chloramphenicol


Listeria monocytogenes

-small gram + rod
-facultatively anaerobic
-blue green sheen on non-blood agar
-Forms Ls and Vs, resembles corynbacteria
-tumbling motility by temperature-sensitive flagella
-grows well in cold
-environmental: found on animals, plants, soil
-intracellular lifestyle protects it from antibodies and complement


Listeria pathogenesis

-infection from environmentally-contaminated food, outbreaks share a common meal/food vendor
-causes gastroenteritis, seldom dangerous to previously-healthy
-patients immunosuppressed including pregnancy
-if immunosuppressed, escapes GI tract, causes complications of pregnancy, meningitis, abcess, endocarditis, spetic arthritis, osteomyelitis, rarely pneumonia
-mortality is 20-30% in immunosuppressed, low mortality in pregnant women but 22% fetal/neonatal death
-in host, prefers to grow intracellularly. Listeriolysin pops phagosome, bacteria escape into cytosol
-cell-cell spread enhanced by polymerization of host actin into rockets


Listeria in Pregnancy

-bacteria escape GI, proliferate in placenta, particularly in 3rd trimester when CMI is lowest
-commonly causes preterm labor, may cause abortion, stillbirth, intrauterine infection


Listeria Treatment

-antibiotics are indicated, IV if CNS or bacteremia
-ampicillin for up to 6 weeks with Gentamicin combo for the first week
-reportable (forms epidermics)


Listeria Prevention

-cook food thoroughly, wash hands, knives, and cutting boards
-wash raw vegetables
-avoid unpastuerized dairy
-if pregnant/ immunocompromised: reheat leftover or ready-to-eat food until steaming (including deli meat) no soft cheeses


Rickettsia Bacteriology

-very short rods
-hard to stain (gram (-)
-all except C burnetti are vectored by arthropods
-vectors: organism that transmits infection between hosts
-reservoir: hosts that are typically infected, maintain infection in environment
-easily enter bloodstream-> bacteremia
-obligate intracellular parasites- cannot reproduce outside a host cell, binary fission inside cells, must grow in tissue culture, eggs, animals


RMSF vector

-Dermacentor variabilis (dog tick) in the eastern United States and Dermacentor andersoni in the Rocky Mountain region and Canada


Rocky Mountain spotted fever pathogenesis

-rickettsia are obligate intracellular parasites: reproduce by binary fission within host cells
-RMSF invades and multiplies in vascular endothelium: virulence factors: OmpA&B: adhesion, Type 4 secretion system: entry, phospholipase A2: escape from endosome, ActA: actin-based cell-cell spread
-rash is caused by leaking from damaged blood vessels


Rocky Mountain Spotted Fever: Diagnosis/ Presentation

-vasculitis-> rash begins on extremities, spreads to trunk
-rash is very common but not universal
-may progress to delerium, coma, DIC, edema, circulatory collapse (18% untreated mortality)
-actually most common on East Coast (dog tick)
-patient may not recall tick bite


Treated for Spotted Fevers

-doxycycline works so well that treatment failure suggests misdiagnosis, but is unsafe in pregnancy
-AAP allows it for children for Rickettsial diseases
-chloramphenicol is alternate for pregnant and allergic patients

-prevention: protective clothing, insect repellent (no tick, no RMSF)


Chlamydia Bacteriology- Life cycle

-dense, rugged elementary bodies (EBs) attach to cell, endocytosed, survive, unpack into reticulate bodies (RBs)
-larger, delicate, RBs replicate, metabolize, pack into EBs, escape host cell
-only EBs are infectious, only RBs divide

-elementary body (EB) attaches to surface of cell
-endocytosis of EB
-EB is in endosome which does not fuse with lysosome
-EB reorganizes into reticulate body (RB) in endosome
-RB replicates by binary fission
-RBs are reorganized to EBs
-Inclusion granule has both RBs and EBs
-some do reverse endocytosis, some do lysis


Elementary bodies (EB)

-small (0.3-0.4 um)
-rigid outer membrane
-bind to receptors on epithelium of lung or mucus membrane and initiate infection


Reticulate bodies (RB)

-non-infectious intracellular form
-metabolically active
-synthesizes its own DNA, RNA, and proteins, but requires ATP from host
-Fragile Gram (-) membrane
-inclusions accumulate 100-500 progeny before release


Pathogenesis of genital chlamydia

-4 million infections per yr: the most common STD in US
-prevalence rates >10% in sexually active adolescent females
-often asymptomatic- particularly in male reservoirs
-most commonly local mucosal inflammation and discharge: urethritis or urethritis/vaginitis/cervicitis
-infection increases risk of acquiring HIV
-pregnant women infected with chlamydia can pass the infection to the infants during delivery
-leading cause of PID and infertility in women
-PID creates risk of chronic pain and ectopic pregnancy


Reiter Syndrome/Reactive Arthritis

-reactive arthritis secondary to an immune-mediated response; Chlamydia is one of several infections known to trigger it
-may present as asymmetric polyarthritis, urethritis, inflammatory eye disease, mouth ulcers, circinate balanitis, and keratoderma blennorrhagica
-80% of affected patients are human leukocyte antigen-B27 (HLA-B27)-positive


Genital Chlamydia Diagnosis: exam

-easily induced endocervical bleeding
-mucopurulent endocervical discharge
-intermenstrual bleeding
-abdominal pain

-urethral discharge
-urinary frequency and/or urgency
-scrotal pain/tenderness
-perineal fullness


Urogenital Chlamydia Diagnosis Lab

-test for co-incident Chlamydia in all STD patients
-option 1: cytologic diagnosis- for infant ocular trachoma, cell sample is stained by Giemsa or IF

-option 2: isolation in cell culture- C. trachomatis grows well in a variety of cell lines, always do culture if the case has legal implications

-option 3: detection of chlamydial ribosomal RNA (rRNA) by hybridization with a DNA probe
-compared to culture: simpler and less expensive, more likely to give a false-positive

-ELISA and PCR from urine or exudate are also options
-serology not useful for C. trachmatis (past infection too common)


Urogenital Chlamydia: Treatment

-chlamydia is intracellular, so antibiotic must be also
-first choice: doxycycline or azithromycin
-Doxycycline is contraindicated in pregnant or s partner(s) also