Pseudomonas (page 3)
© Kenneth Todar, PhD
Dissemination
Blood stream invasion and dissemination of Pseudomonas from
local
sites of infection is probably mediated by the same cell-associated and
extracellular products responsible for the localized disease, although
it is not entirely clear how the bacterium produces systemic illness.
P. aeruginosa is resistant to phagocytosis and the serum
bactericidal
response due to its mucoid capsule and possibly LPS. The proteases
inactivate
complement, cleave IgG antibodies, and inactivate IFN, TNF and probably
other cytokines. The Lipid A moiety of Pseudomonas LPS
(endotoxin)
mediates the usual pathologic aspects of Gram-negative septicemia, e.g.
fever, hypotension, intravascular coagulation, etc. It is also assumed
that Pseudomonas Exotoxin A exerts some pathologic
activity
during the dissemination stage (see below).
Toxinogenesis
Pseudomonas aeruginosa produces two extracellular protein
toxins, Exoenzyme
S and Exotoxin A. Exoenzyme S has the
characteristic subunit structure of the A-component of a bacterial
toxin, and it has ADP-ribosylating activity (for a variety of
eucaryotic
proteins) characteristic of many bacterial exotoxins. Exoenzyme S is
produced by bacteria
growing in burned tissue and may be detected in the blood before the
bacteria
are. It has led to the suggestion that exoenzyme S may act to impair
the function
of phagocytic cells in the bloodstream and internal organs as a
preparation for
invasion by P. aeruginosa.
Exotoxin A has exactly the same mechanism of action as the
diphtheria
toxin; it causes the ADP ribosylation of eucaryotic elongation factor
2 resulting in inhibition of protein synthesis in the affected cell.
Although it is partially-identical to diphtheria toxin, it is
antigenically-distinct.
It utilizes a different receptor on host cells than diphtheria toxin,
but otherwise it enters
cells in the same manner and has the exact enzymatic
mechanism. The production of Exotoxin A is regulated by exogenous iron,
but the details of the regulatory process are distinctly different in
C.
diphtheriae and P. aeruginosa.
Exotoxin A appears to mediate both local and systemic disease processes
caused by Pseudomonas aeruginosa. It has necrotizing activity
at
the site of bacterial colonization and is thereby thought to contribute
to the colonization process. Toxinogenic strains cause a more virulent
form of pneumonia than nontoxinogenic strains. In terms of its systemic
role in virulence, purified Exotoxin A is highly lethal for animals
including
primates. Indirect evidence involving the role of exotoxin A in disease
is seen in the increased chance of survival in patients with
Pseudomonas
septicemia that is correlated with the titer of anti-exotoxin A
antibodies
in the serum. Also, tox- mutants show a reduced virulence in
some models.
Table 1 (below) is a summary of the virulence determinants of
Pseudomonas aeruginosa. Table 2 (next page) is a brief
description of the
diseases
caused
by Pseudomonas aeruginosa.
Table 1.
Summary of the Virulence
Determinants of Pathogenic Pseudomonas aeruginosa
Adhesins
pili (N-methyl-phenylalanine pili)
polysaccharide capsule (glycocalyx)
alginate slime (biofilm)
Invasins
elastase
alkaline protease
hemolysins (phospholipase and lecithinase)
cytotoxin (leukocidin)
siderophores and siderophore uptake systems
pyocyanin diffusible pigment
Motility/chemotaxis
flagella
Retractile pili
Toxins
Exoenzyme S
Exotoxin A
Lipopolysaccharide
Antiphagocytic surface properties
capsules, slime layers
LPS
Biofilm construction
Defense against serum bactericidal reaction
slime layers, capsules, biofilm
LPS
protease enzymes
Defense against immune responses
capsules, slime layers, biofilm
protease enzymes
Genetic attributes
genetic exchange by transduction and conjugation
inherent (natural) drug resistance
R factors and drug resistance plasmids
Ecological criteria
adaptability to minimal nutritional requirements
metabolic diversity
widespread occurrence in a variety of habitats
Pseudomonas aeruginosa
Scanning electron micrograph. CDC
chapter continued
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