Campylobacters

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Campylobacters
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Human pathogens

• Gram-negative rods with comma, S shapes
• Motile, with a single polar flagellum
• Do not produce spores
• Campylobacter jejuni and Campylobacter coli
• Cause enteritis and systemic infection (rarely),
  diarrhoea and abdominal pain
• The main route of transmission is generally
  believed to be foodborne, via undercooked meats
  and meat products, as well as raw or contaminated
  milk. The ingestion of contaminated water or ice
  is also a recognized source of infection.

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Figure 2. Scanning electron microscope image of
Campylobacter jejuni, illustrating its corkscrew
appearance and bipolar flagella. Source
Virginia-Maryland Regional College of Veterinary
Medicine, Blacksburg, Virginia.
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Figure 1. Cases of Campylobacter and other
foodborne infections by month of specimen
collection
Campylobacter jejuniAn Emerging Foodborne
Pathogen Sean F. Altekruse, Norman J. Stern,
Patricia I. Fields, and David L. Swerdlow
U.S. Food and Drug Administration, Blacksburg,
Virginia, USA U.S. Department of Agriculture,
Athens, Georgia, USA and Centers for Disease
Control and Prevention, Atlanta, Georgia, USA
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Pathogenesis

• The campylobacters have LPS with endotoxic
  activity
• Cytopathic extracellular toxins and enterotoxins
  have been found, but have yet to be significant
  in human disease.
• About 104 organism is necessary to produce
  infection
• Acquired by the oral route from food/drink ?
  multiply in small intestine and invade the
  epithelium ? RBCWBC in stools

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Bacteria that act as carcinogens?

• Helicobacter pylori

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Helicobacter pylori

• Spiral-shaped Gram-negative rod
• Antral gastritis, duodenal ulcer disease, gastric
  ulcers, gastric carcinomas
• Morphologically, many common characteristics with
  campylobacters
• Has multiple flagella at one pole and is actively
  motile
• A strong producer of urease

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Bacteria and Idiopathic Diseases

• Speculation that bacteria may be involved in the
  pathology of idiopathic diseases
• H. pylori is now firmly linked to the
  pathogenesis of stomach ulcers
• Gastric ulcer formerly was believed to be due
  solely to stressful living, and was treated by
  histamine receptor antagonists
• Now, treatment is by antibiotics to kill H.
  pylori ? triple therapy
• metronidazole
• bismuth subsalicylate/ bismuth subcitrate
• amoxicillin / tetracycline
• Hypothesis a growing no. of bacteria have the
  ability to control the cell cycle and apoptosis

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Pathogenesis

• Grown at pH 6-7, killed at acid pH within gastric
  lumen
• gastric mucus is impermeable to acid and has a
  strong buffering capacity lumen pH 1-2
  epithelial side pH 7.4
• Urease yields production of ammonia for further
  buffering of acid
• H. pylori is quite motile, even in mucus
• Mechanisms on how H. pylori adheres to gastric
  mucosa has yet to be elucidated
• Mechanisms on how H. pylori causes mucosal
  inflammation and damage are not well defined

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Pseudomonas aeruginosa
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Pseudomonas

• Gram negative bacteria
• Rod-shaped, polar flagella (hence, motile, as
  well as its role in adhesion)
• Inhabit the soil and water
• Pseudomonas aeruginosa is the most prevalent
  opportunistic pathogen
• Intrinsically resistant to many antibiotics ?
  nosocomial infection
• combinations gt2 drugs (eg. Penicillin
  aminoglycoside)

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P. aeruginosa

• Obligate aerobe
• Produce a sweet or grape-like smell
• Colonies with a fluorescent greenish colour,
• nonfluorescent bluish pigment pyocyanin
• greenish pigment pyoverdin
• dark red pigment pyorubin
• black pigment pyomelanin

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Pathogenesis

• P. aeruginosa is only pathogenic when introduced
  into areas of devoid normal defenses Pili
  (fimbriae) promote attachment
• Exotoxin A causes necrosis, blocks protein
  synthesis (? DTx)
• Alginate, an exopolysaccharide is important in
  adhesion of P. aeruginosa to tracheal and buccal
  cells.
• antibodies to the alginate inhibit buinding of
  the organism to tracheal cells

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Case Study
A 48 year old Caucasian male presented to the
emergency room after a progressive history of
left foot cellulitis. The patient works as an
oil-field worker and began experiencing left foot
erythema and blisters. -- progressed to increased
erythema and a green-yellowish drainage from the
digits and in between the toes.

• Medical history. abuse alcohol ,drug abuse when
  he was in his 20s. His family history includes
  diabetes mellitus. His x-ray report reveals no
  signs of gas in the tissue and no signs of
  osteomyelitis.
• His culture report revealed 3 tiny gram negative
  rods and 1 gram positive cocci. On day 1,
  presumptive 4 Pseudomonas aeruginosa was
  identified.
• In the photo on left, it is interesting how just
  his left foot is infected and his right foot is
  completely spared.
•  

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Discussion and Treatment

• Host does not initially appear to be
  immunocompromised. However, he has a history of
  drug use and consumes alcohol quite heavily
  during the week. His work conditions are also
  conducive to these type of infections wears
  steel toe type boots and rubber-type boots in the
  field. Soil contaminates and moisture would play
  an important role in pathogenesis of this
  infection.
• The patient also had exposure to Bactrim early in
  his treatment which may have played a role in the
  ability of his immune system to fight the
  infection in its early stage. Two extracellular
  proteases and extracellular protein toxins are
  produced in the initial infective stage. Elastin
  protease and alkaline protease destroy the cells
  ground substance and lysis its supporting
  structure of fibrin and elastin. Exotoxin A has a
  tissue necrotizing effect and has the same
  mechanism of action as the diphtheria toxin.
  Exoenzyme S is also thought to be a tissue
  destructive exoenzyme that is commonly seen
  during pseudomonas colonization on burn wounds.

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The picture at left represents local colonization
of pseudomonal infection of the foot. Here, the
skin is erythematous and has a scalded-skin type
appearance. This is likely due to extracellular
toxins and proteases causing local ground
substance disruption. You can also readily see
the alginate slime layer that forms a matrix of
the pseudomonas biofilm. This alginate biofilm is
representative of pseudomonas colonization and
the bacterial attempt at protecting the colony
from host defenses. Treatment should include
primary coverage for pseudomonal infection.
Sensitivity reports revealed bacteriocidal
activity using Ciprofloxacin.
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P. aeruginosa and Cystic Fibrosis

• Cystic fibrosis, an autosomal recessive disease
  and the most common genetic lesion in Caucasians
• Caused by mutations in the gene encoding the
  cystic fibrosis transmembrane conductance
  regulator (CFTR) a Cl- channel located in the
  apical membrane of epithelial.
• Results in the formation of mucin at epithelial
  surfaces which has an increased NaCl content and
  unusually thick ? clearing of bacteria becomes
  less efficient
• Hence, patients are susceptible to colonisation
  with P. aeruginosa. Recurrent infections
  produces progressive damage to the lungs.

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P. aeruginosa and Human Defensin

• But healthy friends and families who are exposed
  to aspirated bacteria of CF patients remain
  unaffected.
• P. aeruginosa has been suggested to be sensitive
  to some cationic antimicrobial peptides, due to
  high ionic strength. Human ?-defensin 1 is
  produced by lung epithelia.
• So healthy individuals rapidly kill these
  organisms.
• But when CFTR was transfected into CF airway
  epithelia, correcting the fault in the NaCl
  balance, the bacteria were killed
• This suggested that the failure to kill bacteria
  by the antimicrobial peptides was salt-dependent.
  High salt concentration in CF patients makes the
  antimicrobial peptides non-functional.

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Burkholderia pseudomallei

• Small, motile, aerobic Gram-negative bacillus
• Colonies are mucoid and smooth to rough and
  wrinkled in cream to orange colour.
• Melioidosis of humans, in SE Asia and northern
  Australia
• high mortality rate if untreated
• surgical drainage of localised infection may be
  necessary