17. Persistent bacterial infection

Question 1

How does a persistent infection differ from an acute infection?

Answer 1

some bacteria remain and resist the immune system
immune status quo established

Question 2

what 7 things drive persistence?

Answer 2

1. Colonisation of specific site
2. Modification of intracellular environment
3. Host mimicry
4. Resistance to immune effector mechanisms
5. Anti-phagocyte defence
6. Selective gene inactivation
7. Antigenic variation

Question 3

what is Lyme disease?

Answer 3

first described in 1977 while investigating juvenile arthritis
most prevalent tick-borne illness in US, Europe and Asia
skin, nervous system, heart and joints
bimodal age distribution
transmitted by Ixodes tick when feeding

Question 4

what causes Lyme disease?

Answer 4

Borrelia burgdorferi (main one)
Borrelia garinii
Borrelia afzelii

Question 5

what is Borrelia burgdorferi?

Answer 5

is a spirochaete
motile
spiral structure flagella enclosed between the membranes
distinct morphology

Question 6

What is the Ixodes tick life cycle?

Answer 6

2 year life cycle
4 development forms
eggs laid in spring and hatch in summer
larva becomes infected when it feeds from infected organism
Nymph takes blood meal through the next spring
adults feed and mate during next summer and autumn
then lay eggs

Question 7

What are the 4 developmental forms of the Ixodes Tick?

Answer 7

Eggs, Larva, Nymph, Adults

Question 8

What form of the Ixodes Tick is primarily responsible for transmission to humans?

Answer 8

The Nymph
due to human mostly being outside in the spring and summer
need to feed for 36-48 hours to transmit infection

Question 9

What is the early stage of Lyme disease?

Answer 9

localised infection
expanding rash from bite - erythema migrans
lasts 3-4 weeks

Question 10

what is the dissemination stage of Lyme disease?

Answer 10

in the weeks following initial infection
spread haematogenously to body tissues
multiple rashes
fatigue, chills, headache, fever, joint pain, swollen lymph nodes
can persist for 3 months

Question 11

what is post-treatment Lyme disease syndrome (PTLDS)?

Answer 11

Disabling symptoms lasting more the 6 months
joint pain, cognitive issues, fatigue
no evidence of active infection so a question of if its actually caused by Lyme disease

Question 12

What is the pathogenesis of B. burgdorferi?

Answer 12

lipoproteins interact with host immune system (no toxins or LPS)
OspA and OspB stimulate cytokine release and trigger inflammation
disruption of tight junctions
induce break down of ECM
pass between cell endothelial linings into the blood and outrun phagocytes

Question 13

what persistence mechanism does B. burgdorferi have?

Answer 13

OspC lipoprotein binds tick protein SALP15 impairs phagocytosis
BbCRASP binds factor H to inhibit complement activation
Antigenic variation of lipoproteins and surface proteins

Question 14

What is chlamydiaceae?

Answer 14

gram negative
obligate intracellular pathogens

Question 15

what are the relevant 3 species of Chlamydiaceae?

Answer 15

C. trachomatis
C. pneumonia
C. psittaci

Question 16

what disease does C. trachomatis cause?

Answer 16

STI - most common in humans
Trachoma (blindness) - endemic in Africa and Asia

Question 17

what disease does C. psittaci cause?

Answer 17

psittacosis from parrots, pigeons and ducks
flu-like

Question 18

what disease does C. pneumoniae cause?

Answer 18

Pneumonia and respiratory tract infections

Question 19

why is chlamydia an obligate intracellular pathogen?

Answer 19

it cannot make ATP itself

Question 20

What are the 3 developmental forms of chlamydia?

Answer 20

elementary body - non replicating and infectious
reticulate body - replicating and non infectious
Persistent body

Question 21

what is the normal C. trachomatis lifecycle in the cell?

Answer 21

1. elementary body binding to the cell and taken into the endosome
2. elementary body turns into the reticulate and uses ATP from the cell
3. undergoes 8-12 rounds of replication
4. randomly, asynchronously goes back to the elementary body
5. exit the cell via cell lysis or extrusion of the inclusion

Question 22

how is the chlamydia persistent body infection different?

Answer 22

structurally and genetically distinct
survives for many months waiting to reactivate
infected cells constantly producing inflammatory cytokines

Question 23

what are the 2 chlamydia pathogenesis hypotheses?

Answer 23

we don’t actually know what causing the disease pathogenesis
cellular hypothesis
immunological hypothesis

Question 24

what is the chlamydia cellular hypothesis?

Answer 24

chronic proinflammatory cytokines release drives the tissue damage

Question 25

What is the chlamydia immunlogical hypothesis?

Answer 25

the tissue damage is resulted from the host response to the chlamydia proteins

Question 26

what are chlamydia mechanisms of persistence?

Answer 26

enhanced survival inside host cells as it limits exposure to Ig, phagocytes and T and B cells persistent bodies cannot be treated with Ig Type 3 secretion systems inhibit host cell apoptosis diverse surface proteins Ig doesn't prevent reinfection

Question 27

what is Clostridioides difficile?

Answer 27

gram positive Anaerobic rod shaped spore former so it can survive in the environment

Question 28

C.diff infection

Answer 28

a spectrum of disease: mild diarrhoea to pseudomembranous colitis hospital acquired increases when treated with broad-spectrum antibiotics

Question 29

what are the 3 infection outcomes of C. diff?

Answer 29

Asymptomatically colonised by non toxic C. diff Asymptomatically colonised by toxic C. diff and an IgG response present Symptomatic colonised by toxic C. diff and patient cannot mount an immune response

Question 30

what is C. diff toxin induced colitis?

Answer 30

colonisation of the mucus layer TcdA and TcdB encoded by pathogenicity island TcdA binds the apical layer of the epithelium causes glycosylates RhoGTPase disrupts the tight junctions between cells TcdB binds the basolateral side causes neutrophil, epithelial breakdown and pseudomembrane formation

Question 31

what makes up a pseudomembrane?

Answer 31

Immune cells mucus dead epithelium cells

Question 32

what percentage of patients will have reinfection?

Answer 32

20-30% within 2 months

Question 33

what causes the reinfection of C.diff?

Answer 33

relapse a minority due to exogenous infection with spores Antibiotic treatment cannot eliminate C. diff spores

Question 34

what is helicobacter pylori?

Answer 34

a rod bacteria acquired in childhood half the world is infected disease often doesn't develop until adulthood

Question 35

what does helicobacter pylori cause?

Answer 35

gastritis, peptic ulcer disease, gastric cancer

Question 36

what is the only bacteria classed as a class 1 carcinogen?

Answer 36

helicobacter pylori

Question 37

H. pylori pathogenesis: flagella

Answer 37

allows movement through mucus

Question 38

H. pylori pathogenesis: surface adhesins

Answer 38

bind to gastric epithelium BabA BabB

Question 39

H. pylori pathogenesis: secreted enzymes

Answer 39

urease makes ammonia to neutralise stomach pH breakdown of musins so acid comes into contact with the epithelium

Question 40

H. pylori pathogenesis: toxins CagA

Answer 40

Delivered by type 4 secretion system disrupts tight junctions stimulate pro inflammatory cytokines

Question 41

H. pylori pathogenesis: toxins VacA

Answer 41

induces uptake into cells vacuolation apoptosis

Question 42

what is vacuolation?

Answer 42

formation of large vesicles in epithelial cells increase permeability of the epithelial cells disrupts mitochondria and cause apoptosis

Question 43

how does H. pylori persist?

Answer 43

environmental niche - the stomach most immune cells cannot access the stomach due to the harsh environment impairs phagocytic killing evades PRR with not very biologically active LPS VacA blocks antigen dependant T cell proliferation promotes Treg cells

Question 44

how is H. pylori's genetic diversity good for persistence?

Answer 44

adapts constantly changing bodies and antigens naturally competent cells that can take up DNA from other bacteria easily