Intracellular Bacteria Flashcards
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
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
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
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
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
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)
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
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
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
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
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)
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
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
14
Q
RMSF vector
A
-Dermacentor variabilis (dog tick) in the eastern United States and Dermacentor andersoni in the Rocky Mountain region and Canada
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
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
