What’s PSEUDOMONAS aeuroginosa?
-gram neg bacillus rods
-found in soil and water (ubiquitous)
-motile
* via one or several flagella or polar pili (twitching)
-aerobic (this specifically)
* some strains grow anaerobically by nitrate respiration
-these colonies make water-soluble pigments that functions as anti-bacterials
* pyocyanin (blue-green)
* pyoverdin (green)
* fluorescein (yellow flurorescence)
-fruity or grape like odor to colonies ( or near wounds)
-grow very rapidly, very robust
-needs minimal nutritional requirement
*non-fermentative
~ indophenol oxidase (just like neisseria sp.)
* needs only acetate and ammonia as carbon and nitrogen sources
~ most organic compounds can provide this including petroleum and toxic wastes
-can survive in hand creams, soaps, and dilute antiseptics
What are PSEUDOMONAS virulence factors : persistence?
- mucoid polysaccharide capsule (alginate) shields from immune system
- siderophores
- elastase
- exotoxin A
- phospholipase C
What are PSEUDOMONAS virulence factors: dissemination?
- toxin A
- collagenase
- elastase
- exoenzyme
- flagella
- heat stable hemolysin
- tissue damage by proteases and toxins
What are PSEUDOMONAS virulence factors: nutritional aids?
-siderophores (iron binding compounds):
* compete with transferrin for iron
* iron limitation causes increases production of elastase and exotoxin A
~ damages tissues or creates conditions that make iron more accessible
-phospholipase C:
* hydrolyze phospholipids (lecithin) in the eukaryotic membrane, releasing usable phosphate
How do you encounter PSEUDOMONAS and how does it enter?
-encounter
* adheres to vegetables and plant matter
* in water taps, drains, wet surfaces
~ otitis externa - swimmer’s ear
* hot tubs! (folliculitis, dermatitis)
~ “hot tub rash”
~ 10^8 organisms/mL
-opportunistic pathogen:
* local or systemic breach of immune system
* immunocompromised patients
-organism doesn’t adhere well to healthy epithelium
* can enter through abrasions, cuts, etc
* usually they don’t get far unless in large numbers
-after entry, ability to spread and multiply depends on two things:
* avoiding phagocytosis
* successful adherence to a surface
-adherence to epithelia is mediated by flagella and pili
* interactions with glycolipid (cleaves sialic acid to create asiago GM1; receptor for Type 4 pili) on host cells and toll like receptors (TLR5)
What are the hospital acquired infections?
- frequent cause of nosocomial infections
- regional incidence (%) of pathogens isolated from patients with hospital-acquired pneumonia (HAP)
- PSEUDOMONAS aeuroginosa is the second most HAP in USA after staphylococcus aureus
how does PSEUDOMONAS cause damage?
-LPS
* adhesin
* Lipid A = endotoxin
~ interacts with host TLR4 to initiate inflammatory response
- fever, hypotension (low blood pressure), gm - sepsis
- less inflammatory than E. coli or S. typhimurium
* core oligosaccharide interacts with CFTR (an ATP binding cassette transporters; cystic fibrosis transmembrane conductance regulator)
~ bacterial internalization, initiation of immune resistance
* Long O-antigen side chains
~ responsible for resistance to human serum, antibiotics detergents
- exotoxins (cause local inflammation)
* some kill host cells (exotoxin A)
~ ADP-ribosylation of EF -2 (similar to diphtheria toxin)
* all are tightly regulated
-multifunctional enzymes (proteases)
* elastase
~ cleaves elastin and collagen - direct tissue damage
~ cleaves proteinase inhibitors
~ cleaves immune system components
- complement and immunoglobulins
* LasA
~ serine protease that works with elastase to degrade elastin
-Type III secretion system
* delivers virulence factors directly into host cells
~ transfer from bacterial cytosol to host cytoplasm
* some components are similar to flagella
*target specific proteins on host cells
*induced by host cell contact or low calcium levels
What are some predisposing factors of PSEUDOMONAS
local breach of the immune system: - cystic fibrosis - trauma - IV drug abuse systemic - neutropenia - diabetes - premature infants and neonates both systemic and local - burns
What’s cystic fibrosis?
- P. aeuroginosa doesn’t adhere well to normal intact epithelium
- ciliated strains adhere better than non-ciliated strains
- cystic fibrosis respiratory cells bind more P. aeroginosa than those of normal cells
- thickened mucus inhibits oral ciliary clearance function
What’s CFTR?
- cystic fibrosis transmembrane conductance regulator
- located on human chromosome 7
- dysfunctional in CF patients
- loss of Cl- transport
- hereditary
- F508 most common mutation
- can be rescued with normal copy of gene
What’s cystic fibrosis?
- CFTR may cause decreased sialylation of surface glycolipids
- P. aeruginosa binds to these asiago-glycolipds
- dehyrdation of respiratory secretions
- thick mucosa produced which impairs mucociliary system
- mucoid expo polysaccharide (alginate) shields organism from immune system
- however, these alginate strains produce less protease and toxins
What’s P.aeruginoa biofilm formation?
- p. aeroginosa forms biofilms within the lungs
- communities of bacterial cells that reside within a extracellular matrix
- bacteria within biofilms are recalcitrant to antibiotic treatments and more resistant to host defenses
- biofilm formation contributes to chronic nature of pseudomonas infections
What’s PSEUDOMONAS and sepsis?
-LPS (endotoxin) mediated
* specifically lipid A moiety
* triggers production of tumor necrosis factor (TNF)
~ TNF stimulates macrophages to produced interleukin- 1beta (IL-1)
What’s sepsis?
- sever systemic illness marked by hemodynamic derangements and organ malfunction brought about by the interaction of certain microbial products with host reticuloendothelial (macrophage) cells
- MODS (multi-organ dysfunction syndrome)
- high cardiac output, lowered blood pressure
- distributive shock (lack of perfusion of selected vascular beds)
- 3 requirements:
- large population of infecting/colonizing organisms
- presence of bacterial products that stimulate release of host cytokines
- widespread dissemination of microbial products to host’s reticuloendothelial system (macrophages, monocytes)
What are the mortality rates of PSEUDOMONAS?
- depends on:
- nature and severity of infection
- host defense state
- promptness and efficacy of treatment
- neutropenic patients: 50-70% mortality
- PSEUDOMONAS endocarditis: up to 50% mortality
- sepsis that reaches shock stage: >50% mortality
What’s the diagnosis and treatment of PSEUDOMONAS?
- easily cultured and identified
- antibiotic treatment depends on the geographic locale:
- in some hospitals certain antibiotic-resistant strains predominate
- resistance is due to limited permeability of outer membrane, efflux pumps, and antibiotic resistance genes
- frequently requires antibiotic synergism to treat
