bacterial pathogens and disease I

Question 1

describe virulence mechanisms

Answer 1

adherence factors = proteins
biofilms
invasion of host cells and tissues
toxins = endotoxins and exotoxins

Question 2

what are exotoxins

Answer 2

heterogenous groups of proteins produced and secreted by living bacteria cells
produced by both gram negative and positive bacteria
cause disease symptoms in host during disease
act via a variety of diverse mechanisms

Question 3

why have exotoxins

Answer 3

cause disease so can help with transmission of disease
in severe disease the host may be literal and evolutionary dead end
too many toxins = disease causing activity may not be the primary function
can evade immune response, enable biofilm formation, attachment to host cells and escape from phagosomes
allow for colonisation, niche establishment and carriage advantage

Question 4

cause of staphylococcus aureus

Answer 4

produces haemolytic toxins
causes cells to lyse by forming pores
important features of s.aureus disease

Question 5

what do phenol soluble modulines PSM do

Answer 5

aggregate the lipid bilayer of host cells

Question 6

genetics of exotoxins

Answer 6

can be encoded by chromosomal genes shiga toxi
many toxins coded by extrachromosmal genes
plasmids = bacillus anthracis toxin, tetanus toxin
lysogenic bacteriophage = streptococcal pyrogenic exotoxins in scarlet fever

Question 7

classification of exotoxins

Answer 7

1. membrane acting toxins = type 1
2. membrane damaging toxins = type 2
3. intracellular toxins = type 3

Question 8

describe type 1 exotoxin

Answer 8

act from without the cell
interefere with host cell signalling by innapropriate activation of host cell receptors
target receptors guanylyl cyclase = increased intracellular cGMP, adenyl cyclase = increased intracellular cAMP, rho proteins and ras proteins

Question 9

describe type 2 exotoxins

Answer 9

cause damage to host cell membrane

1. insert channels into host membrane = b-sheet toxins and alpha helix toxins
2. enzymatic damage e.g. PSM

or receptor mediated or independent
e.g membrane damaging toxins

Question 10

type 3 exotoxins

Answer 10

active within the cell, but need to enter cell first 
usually 2 components: AB toxins 
receptor binding and translocation = B 
toxigenic = A 
may be single or multiple B untis

Question 11

enzymatic component A activities

Answer 11

1. ADP - ribosyl transferases
2. glucosyltransferases
3. deamidase
4. protease
5. adenylcyclase

Question 12

what are superantigens and inflammatory cytokines

Answer 12

exotoxins can induce inflammatory cytokine release
IL1, IL1B,IL6, interferon gamma and iL18
superantigen = non specific bridging of the MHC class II and t cell receptor leading to cytokine production
via activation of diff inflamasome = leads to cytokines such as IL8

Question 13

describe toxoids, vaccine and antibodies

Answer 13

toxins can be inactivated using formaldehyde or glutaraldehyde

toxoids = inactive proteins, but highly immunogeneic = form basis for vaccines e.g. tetanus vaccine

treatment for toxin mediated disease can be affected by administering performed antibodies to the toxin
experimental and research = monoclonal antibodies

Question 14

toxins in clostridium difficle

Answer 14

gram positive bacillus 
anaerobic
spore forming 
toxin producing 
can be carried asymptomatically in gut 
3 toxins 
spread by ingestion of pores, remains dormant in environemnt

risk factors = antibiotic use, age, antacids, prolonged hospital stay

Question 15

clostridium difficile - antibiotics

Answer 15

act by disrupting microbial ecosystem within gut
antibiotics provide competitve advantage to spore forming anaerobes over nonforming
allows c.difficile colonisaton and growth
all antibiotics have potential for causing disease
some antibiotics worse than other incl: 2/3rd gen cephalosporins, quinalone, clindamycin

Question 16

c.difficile symptoms

Answer 16

begins asymptomatic 
pathcy necrosis with neutrophil infiltration 
epithelial ulcers
pseudomembranes 
watery diahorrhea

Question 17

describe 2 phase test

Answer 17

1. glutamate dehydrogenase = detects c.difficile organism
2. toxin enzyme linked immunosorbent assay for TcdA and TcdB toxins
3. detection of tcda and tcdb genes = PCR
4. colonoscopy = pseudomembranous colitis

Question 18

treatment for c.difficle

Answer 18

removal of offending antibiotics fidaxomicin or metronidazole or vancomycin
surgery = partial/colectomy
recurrent = faecal transplant

Question 19

escherichia coli disease

Answer 19

VTEC or shiga-toxin producing e.coli
stx carried by some e.coli
identified by growth on sorbitol macconkey agar = doesnt ferment sobital and is clear
other less common type not identified using SMAC
transmitted via consumption of contaminated food/water
very low infectious dose

Question 20

pathogenesis toxin

Answer 20

toxin = shiga like toxin = verocytotoxin
stx,stx1, 1a, 1c,1d, stx2a,2c,2d

gene carried on lysogenic virus
type 3 exotoxin = AB5

enzymatic component a = N-glycosidase

Question 21

how does pathogenesis toxin work?

Answer 21

1. binds to receptor globotriaosylceramide GB3 or globotetraosylceramide on host membrane
2. bound toxin internalised by receptor mediated endocytosis
3. carried by retrograde trafficking via golgi to ER
4. a subunit cleaved off by membrane bound proteases
5. once in cytoplasm A1 and A2 dissociate
   A1 binds to 28S RNA subunit = blocks protein synthesis

Question 22

STEC pathogenesis

Answer 22

stec adheres to epithelial cells of gut mucosa
stx is transported from intestine to kidney and other tissues
binds to glomerular endothelial cells of kidney, cardiovascular and CNS system
v high levels of GB3 in kidney, kidney is v affected
stx favours inflammation = microvascular thrombosis and inhibition of fibrinolysis