Intracellular Bacteria

Question 1

major intracellular pathogens

Answer 1

• Neisseria
• Enterics-Shigella, E coli, salmonella, yersinia
• mycobacter
• some bacilli (anthrax)
• legionella
• listeria
• rickettsial-rickettsia, ehrlichia, anaplasma and C burnetti
• chlamydia
• some systemic fungal infections-histoplasma, cryptococcus
• all viruses

Question 2

obligate intracellular

Answer 2

• chlamydia

- Rickettsial-rickettsia, ehrlichia, anaplasma, c burnetti

Question 3

facultative intracellular

Answer 3

• legionella
• listeria
• neisseria
• mycobacter
• enterics
• bacilli

Question 4

recurring themes in intracellular pathogenesis 1

Answer 4

• use of infected macrophages for transport
• enterics-typhoid fever
• mycobacter- TB
• fungi-histoplasma

Question 5

recurring themes in intracellular pathogenesis 2

Answer 5

• T3SS
• enhance phagocytosis by target cell type
• alter endosome so that fusion fails
• enterics, legionella, mycobacter

Question 6

recurring themes in intracellular pathogenesis 3

Answer 6

• actin based motility and cell cell spread
• virulence factors with names like ActA
• generate actin tail behind bacteria free in the cytoplasm
• bacteria can eventually ram though cell membrane into next cell
• listeria, shigella

Question 7

recurring themes in intracellular pathogenesis 4

Answer 7

• evasion of humoral immunity, surface defenses
• enterics-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

Question 8

recurring themes in intracellular pathogenesis 5

Answer 8

• effective antibiotic treatment for intracellular replicators must penetrate human cell membrane
• tetracyclines are first choice
• contraindicted in pregnancy
• alternates are azithromycin and chloramphenicol

Question 9

listeria bacteriology

Answer 9

• small gram pos rod
• facultatively anaerobic
• blue green sheen on non-blood agar
• forms Ls and Vs, resembles corynebacteria
• tumbling motility by temperature sensitive flagella
• beta hemolytic
• grows well in cold
• environmental- found on animals, plants, soil
• intracellular life style protects it from antibodies and complement

Question 10

listeria pathogenesis

Answer 10

• infection from environmentally contaminated food, outbreaks share 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, abscess, endocarditis, septic arthritis, osteomyelitis, rarely pneumonia
• mortality is 20-30% in immunosuppressed, low mortality in pregnant women but 22% fetal/neonatal death

Question 11

listeria pathogenesis 2

Answer 11

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

Question 12

listeria treatment

Answer 12

• antibiotics are indicated, IV if CNA or bacteremic
• ampicillin for up to 6 weeks with Gentamicin combo for first week
• reportable because causes epidemics

Question 13

listeria prevention

Answer 13

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

Question 14

Rickettsia bacteriology

Answer 14

• very short rods
• hard to stain-gram neg
• all except c burnetti (Q fever) are vectored by arthropods (reservoirs maintain infection in environment)
• easily enter blood stream
• obligate intracellular-binary fission inside cells, need tissue culture

Question 15

RMSF

Answer 15

• vectored by dog tick
• common in eastern US
• invades and multiplies in vascular endothelium
• virulence factors OmpA&B, T4SS, Phospholipase A2, ActA all cause blood vessels to burst and make tiny dots that is the rash

Question 16

Omp A and B

Answer 16

adhesion

Question 17

T4SS

Answer 17

entry into cells

Question 18

phospholipase A2

Answer 18

escape from endosome

Question 19

ActA

Answer 19

actin based cell cell spread

Question 20

RMSF diagnosis

Answer 20

• headache
• fever
• myalgia
• vasculitis-rash begins in extremities and spreads to trunk-common but not universal
• may progress to delerium, coma, DIC, edema, circulatory collapse (18% untreated mortality)
• actually most common on east coast
• patient may not recall tick bite
• can be diagnoses immunochemically in lab

Question 21

treatment for spotted fever

Answer 21

• doxycycline works so well that treatment failure suggests misdiagnosis but unsafe in pregnancy
• AAP allows for chilren
• chloramphenicol is alternate for pregnant and allergic
• prevention-protective clothing and insect repellant

Question 22

chlamydia replication

Answer 22

• elementary body gets into cell, in endosome, prevents fusion via its T3SS
• elementary body changes to reticulate body
• reticulate body divides and multiplies
• some change back to EBs
• inclusion granule has both
• can either bud off or burst in cell and cause cell to burst
• reticular bodies don’t survive long on their own

Question 23

elementary bodies

Answer 23

• small
• infectious
• rigid outer membrane
• rugged
• bind to receptors on epithelium of lung or mucus membrane and initiate infection

Question 24

reticulate bodies

Answer 24

• non-infectious intracellular form
• metabolically active
• replicating
• synthesizes its own DNA, RNA, and proteins, but requires ATP from host
• fragile gram neg membrane
• inclusions accumulate 100-500 before release

Question 25

genital chlamydia

Answer 25

- 4 million infections per year-most commong - >10% in sexually active adolescent females - often asymptomatic-male reservoirs - most commonly local mucosal inflammation and discharge-urethritis or vaginitis or cervicitis - infection increases risk of acquiring HIV - pregnant woman infected can pass the infection to their infants during delivery - can lead to PID-chronic pain and ectopic pregnancy - can lead to reactive arthritis

Question 26

reactive arthritis

Answer 26

- secondary to immune mediated response - 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 positive

Question 27

genital chlamydia diagnosis and exam

Answer 27

- women-easily induced endocervical bleeding, mucopurulent endocervical discharge, intermenstrual bleeding, dysuria, abd pain - men-urethral discharge, urinary frequency/urgency, dysuria, scrotal pain/tenderness, perineal fullness

Question 28

urogenital chlamydia

Answer 28

- test for co-incident chlamydia in all STD patients - physical findings are often sufficient for diagnosis, but labs: - cytologic-for infant ocular trachoma, cell sample stained with giemsa or IF - isolation in cell culture-grows well in variety of cell lines, always do culture if case has legal implications - chlamydial ribosomal RNA by hybridization with DNA probe-simpler and less expensive, but more likely to give false positive ELISA and PCR from urine or exudate possible, serology not useful-past infection too common

Question 29

treatment for chlamydia

Answer 29

- intracellular - doxy or azithromycin - erythromycin or amoxicillin-test the cure - can be hidden behind gonococcal-test panel - reinfeciton common-treat partners