campylobacter jejuna Flashcards

1
Q

as a new disease

A
  • campylobacter fetus was well established as a veterinary pathogen in cows/ sheeps and rarely humans
  • in 1972 first report of C.jejuni isolated from faeces of patients with enteritis using a filter technique
  • employed a microaerobic environment
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2
Q

what did Mark Skirrow demonstrate

A
  • 1977
  • demonstrated that campylobacters could be isolated from faeces of patients with diarrhoea using a new method
  • involved a selective antibiotic containing medium and incubation in an atmosphere of 5% oxygen at 43 degrees
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3
Q

campylonacter jejuni - the organism

A
  • gram negative, motile, spiral
  • campylobacter derived from Grek for curved rod
  • microaerophilic - similar to related bacterium helicbacter pylori
  • grows best at 37-42 degrees
  • higher temps are selective and represent higher body temperatures of avian species
  • belongs to epsilon subdivision of the proteobacteria
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4
Q

the disease

A
  • classic symptoms of infection are an acute self limiting gastroenteritis
  • estimated 2-5 days incubation following ingestion
  • sometimes fever
  • typically, 3 -10 days of inflammatory diarrhoea follow with presence of leukocytes
  • can contain blood, pus, mucus
  • abdominal cramping common
  • infection resolves generally without treatment
  • bacteraemia is rare - immunocompromised
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5
Q

what can more serious cases be treated with

A

antibiotics e.g. erythromycin or fluoroquinolones
- resistance is now problematic

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6
Q

diagnosis

A
  • direct microscopy of faecal samples - spiral bacteiral with a characteristic rapid darting motility
  • latex agglutination with specific antisera coated on beads
  • PCR
  • typically based on culture of organism on antibiotic containing selective agar plates incubated at 42 degrees
  • colony morphology, gram stain and phenotypic tests
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7
Q

treatment and resistance

A
  • most of those infected will not seek medical support and infection will resolve
  • staying hydrated is important
  • antibiotics are used for more serious cases
  • typically, macrolides erythromycin and azithromycin or fluoroquinolones typically ciprofloxacin
  • floroquinolone resistance is increasingly problematic
  • multi drug resistance is also emerging
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8
Q

campylobacter in the UK

A
  • commonest cause of bacterial gastroenteritis in the UK
  • estimated 500,000 cases in england and wales annually
  • summer peak is consistent feature around June/ July
  • in low and middle income countries constant exposure to campylobacter is thought to lead to immunity in adults
  • there is significant infant mortality assicated with this endemic infection
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9
Q

campylobacter and chickens

A
  • estimated 70% of campylobacter cases linked to chicken
  • it is commensal in chickens
  • colonise to very high numbers in the chicken caecum
  • carriage is largely asymptomatic
  • no effective strategy to reduce levels of campylobacter in this food product
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10
Q

virulence

A
  • lack of classical virulence features
    -no T3SS though does have flagella based system for injecting proteins
  • no enterotoxins though do produce cytolethal distending toxin
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11
Q

key properties of organism

A
  • cell shape and flagella mediated motility
  • ability to generate cell surface structural diversity for longer term colonisation in animal hosts
  • mimicry of host gangliosides on cell surface by lipooligosaccharide
  • secretion of proteins into host cells via. flagella based secretion system
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12
Q

generating strain diversity - natural transformation

A
  • C.jejuni naturally competent for DNA up take and transformation
  • specific uptake system to transport DNA across membrane barriers into cytoplasm
    RecA recombinase for integration of homologous DNA into the chromosome
  • naturally transformable bacteria recognise closely related DNA through presence of short hyperabundant DNA uptake equences
  • C. jejuni does not use this mechanism to recognise DNA from other campylobacters
  • in contract a campopylobacter transformation system methyltransferase methylates RAATTY sites on C. jejuno DNA and only methylated DNA can transform in campylobacter strains
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13
Q

generating strain diversity - phase variation

A
  • a number of campylobacter genes contain intragenic homopolymeric tracts
  • typically, single nucleotide repeats of 8-12 G or C residues
  • these are error prone during replication so that the number of repeats varies randomly
  • this leads to reversible on-off switching of production of functional protein
  • influence structure of LOS, CPS and flagellin glycan
  • creates extensive surface diversity
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14
Q

C.jejuni lipo-oligosaccharide

A

the C.jejuni outer membrane contains LOS - truncated structure that lacks O antigen which is present in LPS
- terminates in a short oligosaccharide
- in many strains, this region contains unusual sugar sialic acid
- by coating the cell in human ganglioside - lipe epitopes C.jejuni will potentially reduce recognition by the host and consequent immune response
- this can lead to autoimmunity due to production of antibodies against C.jejuni LOS

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15
Q

how many cases can lead to giullain- barre or miller-fish syndrome

A

approx 1 in 1000 cases of C.jejuni infection

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16
Q

Guillan - barre syndrome and C.jejuni

A
  • potenitally life threatening post infectious disease characterised by progressive, symmetrical weakness of the extremities
17
Q

pathogenesis of GBS

A

molecular mimicry of pathogen - borne antigens, leading to generation of cross reactive antibodies that also target gangliosides, is part of the pathogenesis

18
Q

treatments for GBS

A

intravenous immunoglobulin and plasma exchange are proven effective treatments but many patients have considerable residual deficits

19
Q

why does GBS occur

A

GBS typically occurs after an infectious disease in which the immune response generates antibodies that cross react with gangliosides at nerve membranes

  • campylobacter jejuni is the most common infection leading to the infection
20
Q

capsular polysaccharide

A

C.jejuni strains produce an extracellular capsular polysaccharide and can be used to serotype strains
- mutants lacking CPS do not colonise chicks
- lack of CPS also reduces adherence to and invasion of intestinal epithelial cells and serum resistance
- CPS reduces activation of TLR and cytokine stimulation

21
Q

what is CPS composed of

A

composed of a repeating backbone of 2 or more sugars
- this repeat structurally varies in different strains defining serotype

22
Q

what is intrastrain structural variation of CPS due to

A
  • variable modification of the backbone sugars with O-methyl phosphoramidate and O-methyl
  • mediated by phase variable expresssion of MeOPN and O-Me transferase
  • MeOPN can act as bacteriophage receptor and O-Me modification can disrupt bacteriophage docking
23
Q

what systems does C.jejuni contain to glycosylate different proteins

A
  • O- linked protein glycosylation system that specifically modifies flagellins forming the extracellular flagella filament
  • N linked general protein glycosylation system that modifies many extra cytoplasmic proteins
24
Q

O- linked protein glycosylation of C.jejuni flagellin

A
  • as many as 19 serine and threonin residues on the flagellin subunit protein can be modified with unusual monosaccharides pseudaminic acidand legionaminic acid
  • flagellin glycosylation is essential for flagellin to polymerise into the extracellular filament for motility
  • genes involved in flagellin glycosylation vary between strains and phave vary within strains
  • structural variation for flagella tropic phase/ immune system evasion
25
Q

N linked general protein glycosylation system

A
  • modifies over 100 periplasmic and inner/ outer membrane proteins with a conserved heptasaccharide glycan
  • these proteins are modified at a specific asparagine residue within a consensus motif
  • inactivation of glycosylation affects host cell adherence and invasion, colonisation of chicks and mice
  • N linked glycosylation of surface proteins may protect against degradation by extracellular host proteases and enhance protein thermostability