Campylobacters

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.

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.

Figure 1. Cases of Campylobacter and other foodborne infections by month of specimen collection; Campylobacter jejuni—An 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

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  RBC+WBC in stools

Bacteria that act as carcinogens? Helicobacter pylori

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

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

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

Pseudomonas aeruginosa

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 >2 drugs (eg. Penicillin + aminoglycoside)

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

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

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 20’s. 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.  

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.

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.

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.

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.

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