Intracellular Bacteria Flashcards

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1
Q

Major Intracellular Pathogens

A
  • Cocci: Neisseria
  • Enterics: Shigella, E. coli (EIEC), Salmonella, Yersinia
  • Mycobacter
  • Rickettsial: Rickettsia, Ehrlichia, Anaplasma and C. burnetti
  • Listeria- accidental opportunistic
  • Some Bacilli (B anthracis)
  • Legionella
  • Chlamydia
  • Some systemic fungal infections: Histoplasma, Cryptococcus
  • ALL VIRUSES
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2
Q

Obligate vs Facultative Intracellular Parasites

A
  • 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
  • Cocci
  • Enterics (closer to replicating on own)
  • Mycobacteria
  • Bacilli (closer to replicating on own)
  • Listeria
  • Legionella (closer to obligate)
  • Fungi
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3
Q

Recurring theme of bacterial intracellular pathogenesis- macrophages

A
  • use of infected macrophages for transport to target site of infection
  • enterics: typhoid fever
  • Mycobacter: TB
  • Fungi: Histoplasma
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4
Q

Recurring theme of bacterial intracellular pathogenesis- T3SS

A
  • host cell takeover by Type 3 Secretion Systems
  • enhance phagocytosis by target cell type
  • alter endosome so that lysosomal fusion fails
  • Enterics, Legionella, Mycobacter
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5
Q

Recurring theme of bacterial intracellular pathogenesis- Actin based motility

A
  • 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
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6
Q

Recurring theme of bacterial intracellular pathogenesis- humoral immunity

A
  • 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)
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7
Q

Recurring theme of bacterial intracellular pathogenesis- effective antibiotics

A
  • 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
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8
Q

Listeria monocytogenes

A
  • small gram + rod
  • facultatively anaerobic
  • blue green sheen on non-blood agar
  • Forms Ls and Vs, resembles corynbacteria
  • tumbling motility by temperature-sensitive flagella
  • beta-hemolytic
  • grows well in cold
  • environmental: found on animals, plants, soil
  • intracellular lifestyle protects it from antibodies and complement
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9
Q

Listeria pathogenesis

A
  • 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
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10
Q

Listeria in Pregnancy

A
  • bacteria escape GI, proliferate in placenta, particularly in 3rd trimester when CMI is lowest
  • commonly causes preterm labor, may cause abortion, stillbirth, intrauterine infection
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11
Q

Listeria Treatment

A
  • antibiotics are indicated, IV if CNS or bacteremia
  • ampicillin for up to 6 weeks with Gentamicin combo for the first week
  • reportable (forms epidermics)
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12
Q

Listeria Prevention

A
  • 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
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13
Q

Rickettsia Bacteriology

A
  • 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
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14
Q

RMSF vector

A

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

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15
Q

Rocky Mountain spotted fever pathogenesis

A
  • 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
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16
Q

Rocky Mountain Spotted Fever: Diagnosis/ Presentation

A
  • headache
  • fever
  • myalgia
  • 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
17
Q

Treated for Spotted Fevers

A
  • 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)

18
Q

Chlamydia Bacteriology- Life cycle

A
  • 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
19
Q

Elementary bodies (EB)

A
  • small (0.3-0.4 um)
  • infectious
  • rigid outer membrane
  • rugged
  • bind to receptors on epithelium of lung or mucus membrane and initiate infection
20
Q

Reticulate bodies (RB)

A
  • non-infectious intracellular form
  • metabolically active
  • replicating
  • synthesizes its own DNA, RNA, and proteins, but requires ATP from host
  • Fragile Gram (-) membrane
  • inclusions accumulate 100-500 progeny before release
21
Q

Pathogenesis of genital chlamydia

A
  • 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
22
Q

Reiter Syndrome/Reactive Arthritis

A
  • 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
23
Q

Genital Chlamydia Diagnosis: exam

A
  • women:
  • easily induced endocervical bleeding
  • mucopurulent endocervical discharge
  • intermenstrual bleeding
  • dysuria
  • abdominal pain

Men:

  • urethral discharge
  • urinary frequency and/or urgency
  • dysuria
  • scrotal pain/tenderness
  • perineal fullness
24
Q

Urogenital Chlamydia Diagnosis Lab

A
  • 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)
25
Q

Urogenital Chlamydia: Treatment

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