Other members  Burkholderia pseudomallei Melioidosis  Burkholderia mallei Glander  Burkholderia cepacia  Acinetobacter baumannii

Pseudomonas aeruginosa  Gram-negative rod  Opportunistic pathogen Water & soil  Nosocomial infections Immunosuppressive patients  Produces Exotoxin A (PE), in absence of iron  PE inhibits translation elongation in host cell and causes cell death

P.aeruginosa  Motile, strick aerobic, rods, normal flora, growth in 42° & oxidase pos.  Pigmented  Pyocyanin (blue)  Pyoverdin (green and fluorescence)  Pyorubin (red)  Pyomelanin (black)  Fruits odor

Antigens and toxin stracture  Pilus  Slime (alginate & CF patients)  Elastase  Protease  Hemolysin  Exotoxin A

Structural Components  Adherence to host cells mediated by pili and nonpilus adhesins.  LPS (lipopolysaccharide) inhibiting antibiotic killing and suppress neutrophil and lymphocyte activity  Alginate – mucoid exopolysaccharide that forms a shiny biofilm protecting from antibodies, complement, phagocytosis, and antibiotics  Procyanin – impairs ciliary function, mediates tissue damage through production of oxgen radicals

Virulence Factors (toxins and enzymes):  Exotoxin A  Exoenzyme S  Endotoxins  Phospholipase C  Elastase and Alkaline Protease Toxins

Elastase and Alkaline Protease  Destruction of elastin-containing tissues (blood vessels, lung tissue, skin), collagen, immunoglobulins, and complement factors  Can produce hemorrhagic lesions (ecthyma gangrenosum) associated with disseminated infection  Inactivation of interferon and TNF-Alpha

The bug: Pseudomonas aeruginosa  Gram-negative rod  Opportunistic pathogen Water & soil  Nosocomial infections Immunosuppressive patients  Produces Exotoxin A (PE), in absence of iron  PE inhibits translation elongation in host cell and causes cell death

The protein: Exotoxin A  Causes ADP-ribosylation of eEF-2 (eukaryotic elongation factor necessary for translation)  Cell death results  Of interest: acts on same residue of eEF-2 as Diphtheria toxin

Therapeutic applications for Exotoxin A  Used as recombinant immunotoxin to target and kill cancer cells  Can be produced in large quantities in E. coli

Therapeutic applications for Exotoxin A Reiter, Y., Pastan, I. (2008) Trends in Biotechnology. 16,

Clinical Features

Clinical Disease  Pulmonary Infections  Burn Wound Infections and other skin and soft tissue infections (life threatening)  UTI’s (especially catheterized)  External Otitis (malignant OE, swimmer’s ear)  Eye Infections and corneal ulceration via contaminated contact lens cleaning fluids  Pseudomonal Endocarditis

Echtyma Gangrenosum

Malignant Otitis Externa

Pseudomonas Keratitis and Corneal Ulceration

Endocarditis

Mechanisms of Antibiotic Resistance in Pseudomonas aeruginosa

Lab Diagnosis

 Indole test: Negative  Methyl red test: Positive  Voges-Proskauer reaction test: Negative  Citrate utilization test: Positive  Urease test: Negative

 Bacteria show a resistance to antibiotics. Thus, a combination of two or more antibiotics is used to destroy the bacteria. These antibiotics can be given to the patient in orally or intravenously.  Surgery is performed in some cases, where the bacteria has damaged a tissue.  Infections due to pseudomonas aeruginosa can be cured completely in most cases, with the help of medication and surgery Treatment

 Pseudomonal infections are treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside.  Carbapenems (eg, imipenem, meropenem) with antipseudomonal quinolones may be used in conjunction with an aminoglycoside. Treatment

Endocarditis treatment A high-dose aminoglycoside ( tobramycin) and an extended- spectrum penicillin or antipseudomonal cephalosporin (eg, cefepime) are used for 6 weeks.