Pseudomonas
aeruginosa
General
Information
Pseudomonas aeruginosa is the epitome of an opportunistic
pathogen of humans. The bacterium almost never infects uncompromised tissues,
yet there is hardly any tissue that it cannot infect, if the tissue defenses
are compromised in some manner.
Pseudomonas aeruginosa is a Gram-negative, aerobic rod, belonging
to the bacterial family Pseudomonadaceae. These
bacteria are common inhabitants of soil and water. They occur regularly on the
surfaces of plants and occassionally on the surfaces
of animals. Pseudomonas aeruginosa is an opportunistic pathogen that causes
urinary tract infections, respiratory system infections, dermatitis, soft
tissue infections, bacteremia and a variety of
systemic infections, particularly in patients with severe burns, and in cancer
and AIDS patients who are immunosuppressed. Pseudomonas aeruginosa
is occasionally a pathogen of plants, as well.
Pseudomonas
bacterium in nature might be found in a biofilm,
attached to some surface. Pseudomonas aeruginosa is motile by means of a single polar
flagellum. P. aeruginosa can live in a biofilm form, or it can live in a planktonic
form, as a free-swimming cell. Its optimum temperature for growth is 37
degrees, and it is able to grow at temperatures as high as 42 degrees.
P. aeruginosa produces two types of soluble pigments, pyocyanin and pyoverdin. The
latter is produced abundantly in media of low-iron content, and could function
in iron metabolism in the bacterium. Pyocyanin refers
to "blue pus" which is a characteristic infections caused by Pseudomonas aeruginosa.
Pseudomonas aeruginosa is notorious for its resistance to
antibiotics and is, therefore, a particularly dangerous and dreaded pathogen.
The bacterium is naturally resistant to many antibiotics due to the permeabiliity barrier afforded by its outer membrane LPS.
Also, its tendency to colonize surfaces in a biofilm
form makes the cells impervious to therapeutic concentrations antibiotics.
Moreover, Pseudomonas maintains antibiotic resistance plasmids, and it is able
to transfer these genes my means of the bacterial processes of transduction and
conjugation. Only a few antibiotics are effective against Pseudomonas,
including fluoroquinolones, gentamicin
and imipenem, and even these antibiotics are not
effective against all strains. The futility of treating Pseudomonas infections
with antibiotics is most dramatically illustrated in cystic fibrosis patients,
virtually all of whom eventually become infected with a strain that is so resistant
that it cannot be treated.
According to the
CDC, the overall incidence of P. aeruginosa
infections in US hospitals averages about 0.4 percent (4 per 1000 discharges),
and the bacterium is the fourth most commonly-isolated nosocomial
pathogen accounting for 10.1 percent of all hospital-acquired infections. (1) (2)
Pathogenesis
For an opportunistic pathogen such as Pseudomonas aeruginosa,
the disease process begins with the evasion of normal host defenses. The
pathogenesis of Pseudomonas infections is caused by many virulence determinants
possessed by the bacterium. Multiple and diverse determinants of virulence are
expected in the wide range of diseases caused by Pseudomonas aeruginosa such as
Pseudomonas septicemia, urinary tract infections, Pseudomonas pneumonia and
chronic lung infections, endocarditis, dermatitis,
and osteochondritis.
Most Pseudomonas
infections are both invasive and toxinogenic. The
Pseudomonas infection has three distinct stages: (1) bacterial attachment and
colonization; (2) local invasion; (3) disseminated systemic disease. However,
the disease process may stop at any stage. Particular bacterial determinants of
virulence mediate each of these stages and are ultimately responsible for the
characteristic syndromes that accompany the disease. (1)
Colonization
The fimbriae of Pseudomonas will adhere to the epithelial cells
of the upper respiratory tract and, by inference, to other epithelial cells as
well. These adhesins appear to bind to specific galactose or mannose or sialic
acid receptors on epithelial cells. Colonization of the respiratory tract by
Pseudomonas requires fimbrial adherence and may be
aided by production of a protease enzyme that degrades fibronectin
in order to expose the underlying fimbrial receptors
on the epithelial cell surface.
The receptor on
tracheal epithelial cells for Pseudomonas pili is
probably sialic acid (N-acetylneuraminic
acid). Besides pili, there are possibly two other
cell surface adhesins utilized by Pseudomonas to
colonize the respiratory epithelium or mucin. (1)
Invasion
The ability of Pseudomonas aeruginosa
to invade tissues depends upon its resistance to phagocytosis
and the host immune defenses, and the extracellular
enzymes and toxins that break down physical barriers and otherwise contribute
to bacterial invasion. As mentioned above, the bacterial capsule or slime layer
effectively protects cells from opsonization by
antibodies, complement deposition, and phagocyte engulfment.
Two extracellular proteases have been associated with virulence
that exert their activity at the invasive stage: elastase and alkaline protease. Elastase
has several activities that relate to virulence. The enzyme cleaves collagen, IgG, IgA, and complement. It also
lyses fibronectin to expose receptors for bacterial
attachment on the mucosa of the lung. Elastase
disrupts the respiratory epithelium and interferes with ciliary
function. Alkaline protease interferes with fibrin formation and will lyse fibrin. Together, elastase
and alkaline protease destroy the ground substance of the cornea and other
supporting structures composed of fibrin and elastin.
Elastase and alkaline protease together are also
reported to cause the inactivation of gamma Interferon (IFN) and Tumor Necrosis
Factor (TNF).
P. aeruginosa produces three other soluble proteins
involved in invasion: a cytotoxin and two hemolysins. The cytotoxin is a
pore-forming protein. It Of the two hemolysins, one is a phospholipase
and the other is a lecithinase. They appear to act
synergistically to break down lipids and lecithin. The cytotoxin
and hemolysins contribute to invasion through their cytotoxic effects on eukaryotic cells.
The Pseudomonas
pigments are probably determinants of virulence for the pathogen. The blue
pigment, pyocyanin, impairs the normal function of
human nasal cilia, disrupts the respiratory epithelium and exerts an
inflammatory effect on phagocytes. A derivative of pyocyanin,
pyochelin, is a siderophore
that is produced under low-iron conditions to sequester iron from the
environment for growth of the pathogen. No role in virulence is known for the
fluorescent pigment, pyoverdin. (1)
Dissemination
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 reasonable to assume
that Pseudomonas Exotoxin A exerts some pathologic
activity during the dissemination stage. (1)
Toxinogenesis
P. aeruginosa produces two extracellular
protein toxins, Exoenzyme S and Exotoxin
A. Exoenzyme S is probably an exotoxin.
It has the characteristic subunit structure of the A-component of a bacterial
toxin, and it has ADP-ribosylating activity
characteristic of exotoxins. Exoenzyme
S is produced by bacteria growing in burned tissue and may be detected in the
blood before the bacteria are. It has been suggested that exoenzyme
S may act to impair the function of phagocytic cells
in the bloodstream and internal organs to prepare for invasion by P. aeruginosa.
Exotoxin A has exactly the same mechanism of action
as the diphtheria toxin, it causes the ADP ribosylation of eukaryotic elongation factor 2. It utilizes a different receptor on host
cells but otherwise it enters cells in the same manner as the diphtheria toxin
and it has the exact enzymatic mechanism. The production of Exotoxin
A in 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. (1)
Treatment
Obtain at least 2
sets of blood cultures (2 aerobic, 2 anaerobic bottles) from different sites.
In UTI, urinalysis
is helpful in determining a diagnosis.
Obtain Gram stain
of respiratory secretions and cerebrospinal fluid
Antimicrobials are
the main part of therapy. Two-drug combination therapy, such as an antipseudomonal beta-lactam with
an aminoglycoside, can be used. (3)
References:
(1)http://www.wrongdiagnosis.com/
(2)http://www.apic.org/pdf/cdcdefs.pdf
(3)Extensive information on
drugs, diseases, and statistics on Pseudomonas
Pictures:
http://www.uoguelph.ca/~mklub/micro/images.html
http://www2.eckerd.com/RxAdvisor/showmono.asp?monotype=&cpnum=496&match=F
Links:
Extensive information on drugs, diseases, and statistics on Pseudomonas