Intracellular Pathogens Flashcards
What are the major intracellular pathogens (10)?
- Neisseria - diplococci
- Enterics- Shigella, E. coli (EIEC), Salmonella, Yersnia - get around the immune surveilance in the gut - offer self up for immune sampling, induces apoptosis, too. Salmonella tyhpi and the trojan horse
- Mycobacter
- Some bacilli (B. anthracis) - has intracellular trafficking athways, too
- Legionella - has accidental lifecycle in lung -> waters, virulence factors for amoeba work on alveolar macrophages, but if they burn through all the macrophages, can’t survive
- Listeria
- Rickettsia, Ehrlichia, Anaplasma and C. burnetti (rickettsia is the catchall term for intracellular obligate that is not chlamydia)
- Chlamydia
- Some systemic fungal infections: Histoplasma, Cryptococcus
- ALL viruses (because they can’t carry ribosome with them)
What are the obligate intracellular bacterial pathogens?
What is special about culturing them?
- Chlamydia
- Rickettsial : Rickettsia, Ehrlichia, Anaplasma, C.burnetti (Q fever)
NEED TISSUE CULTURE OR CELL CULTURE TO GROW AND BE STUDIED
What are the facultative intracellular pathogens?
Will grow by themselves in the lab, don’t need cells, but will grow in them if available. Larger, looser group
- Legionella (the replication by itself might not be part of the lifecycle, borderline facultative)
- Listeria
- Neisseria
- Mycobacter
- Enterics
What are the recurring themes in intracellular pathogenesis?
- Use of infected macrophages for transport - have seen examples with enteric and mycobacteria (salmonella and TB)
- Host cell takeover by Type 3 Secretion Systems (very important virulence factors) - enhance phagocytosis by target cell type, alter endosome so that lysosome fails to fuse
- Actin-based motility and cell-cell spread (discovered in listeria, rocket behind listeria, pushes you into another cell, NEVER exposed to humoral immunity (complement and antibodies)
- Evasion of humoral immunity, surface defenses (?)
- Effective antibiotics for intracellular replicators MUST penetrate human cell membrane (tetracyclines are the first choice, but contraindicated in pregnancy - alternatives that might not work as well)
Listeria bacteriology Gram? Relationship with oxygen? Hemolytic? What temperature does it grow well in? Where is it found? What are the benefits of its lifestyle?
- Small gram (+)
- Facultatively anaerobic
- Beta-lemolytic (clears)
- Cold, (like salmonella) need to avoid soft cheese and deli meat during pregnancy
- On animals, plants, soil
- Protects it from antibodies and complement
Listeria pathogenesis
What does listeria cause?
Who is at risk and what happens?
- Gastroenteritis, seldom dangerous to previously-healthy
- Patients immunosuppressed, including pregnancy - escapes GI tract, causes complications of pregnancy, meningitis, abscess, endocarditis, septic arthritis, osteomyelitis, rarely pneumonia - mortality is 20-30% in immunosuppressed, low mortality in pregnant women, but 22% fetal/neonatal death
What happens to women with listeria during 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
How do you treat listeria?
How do you prevent listeria?
- Use IV antibiotics if CNS or bacteremic, ampicillin for up to 6 weeks with Gentamicin combo for the first week
- Cook food thoroughly, wash hands, knives and cutting boards, wash raw vegetables, avoid unpasteurized dairy, if pregnant/immunocompromised, reheat leftover or ready to eat foods until steaming (including deli meat) no soft cheeses
Rickettsia Bacteriology
- What is their morphology and gram stain?
- What is the vector for Rickettsia (except for C. burnetti)
- What is common with rickettsia?
- Obligate or Facultative intracellular parasites?
- very short rods - gram (-)
- arthropods
- Easily enter bloodstream -> bacteremia
- obligate, must grow in tissue culture, eggs, animals WILL NOT GROW ON AGAR
What is the vector for RMSF?
What kind of rash is accompanied?
- dog tick
- Petechial rash - because RMSF invades and multiplies in vascular endothelium, escape from host cell, lyse the cell causing leakage and rash
What is the presentation of RMSF?
Headache; fever; myalgia; vasculitis -> rash begins on extremities, spreads to trunk; rash very common but not universal; may progress to delerium, coma, DIC, edema, circulatory collapse (18% untreated mortality); most common on east coast (dog tick); patient may not recall tick bite
How do you treat for spotted fever?
Doxycycline works well, treatment failure suggests misdiagnosis, UNSAFE in pregnancy, AAP allows it for children for Rickettsial diseases; chloramphenicol is alternate for pregnant and allergic patients; prevent with protective clothing and insect repellent
What is the replication cycle of chlamydia?
Elementary body attaches to surface of cell, endocytosis of EB occurs, EB is in endosome which does NOT fuse with lysosome (T3SS), EB reorganizes into reticulate body (RB) in endosome, RB replicates by binary fission, RBs reorganized to EBs, inclusion has both RBs and EBs, reverse endocytosis or lysis of cells and inclusions - reticulate bodies are easy prey to immune system, elementary seek out new host cell, infectious form
Elementary bodies (chlamydia):
- How big are they?
- Are they infectious?
- Do they have a rigid outer membrane?
- Are they rugged?
- What do they do in life cycle?
- Small
- yes
- Yes
- Yes
- Bind to receptors on epithelium of lung or mucus membrane and initiate infection
Reticulate bodies (chlamydia):
- Are they infectious?
- Do they have a rigid outer membrane?
- What do they do in life cycle?
- No
- No - they have a fragile gram (-) membrane
- Replicate, synthesize their own DNA, RNA, and proteins, but requires ATP from host - inclusions accumulate 100-500 progeny before release
