Frequently acting as an
opportunistic,
nosocomial pathogen of
immunocompromised individuals, but capable of infecting the immunocompetent,
P. aeruginosa typically infects the airway,
urinary tract,
burns, and
wounds, and also causes other
blood infections. It is the most common cause of infections of burn injuries and of the
outer ear (
otitis externa), and is the most frequent colonizer of medical devices (e.g.,
catheters).
Pseudomonas can be spread by equipment that gets contaminated and is not properly cleaned or on the hands of healthcare workers.
Pseudomonas can, in rare circumstances, cause
community-acquired pneumonias, as well as
ventilator-associated pneumonias, being one of the most common agents isolated in several studies.
Pyocyanin is a
virulence factor of the bacteria and has been known to cause death in
C. elegans by
oxidative stress. However,
salicylic acid can inhibit pyocyanin production. One in ten hospital-acquired infections is from
Pseudomonas .
Cystic fibrosis patients are also predisposed to
P. aeruginosa infection of the lungs due to a functional loss in chloride ion movement across cell membranes as a result of a
mutation.
P. aeruginosa may also be a common cause of "hot-tub rash" (
dermatitis), caused by lack of proper, periodic attention to water quality. Since these bacteria thrive in moist environments, such as hot tubs and swimming pools, they can cause skin rash or swimmer's ear. Since pyoverdine is secreted into the environment, it can be easily detected by the host or predator, resulting the host/predator migration towards the bacteria.
Phenazines Phenazines are redox-active pigments produced by
P. aeruginosa. These pigments are involved in
quorum sensing,
virulence, and iron acquisition.
P. aeruginosa produces several pigments all by the same biosynthetic pathway: phenazine-1-carboxamide (PCA), 1-hydroxyphenazine, 5-methylphenazine-1-carboxylic acid betaine,
pyocyanin and aeruginosin A. Two nearly identical operons are involved in phenazine biosynthesis:
phzA1B1C1D1E1F1G1 and
phzA2B2C2D2E2F2G2. The enzymes encoded by these operons convert
chorismic acid to PCA. The products of three key genes,
phzH,
phzM, and
phzS then convert PCA to the other phenazines mentioned above. Though phenazine biosynthesis is well studied, questions remain as to the final structure of the brown phenazine pyomelanin. When pyocyanin biosynthesis is inhibited, a decrease in
P. aeruginosa pathogenicity is observed
in vitro. It has therefore been suggested that pyocyanin is mostly responsible for the initial colonization of
P. aeruginosa in vivo.
Plants and invertebrates In higher plants,
P. aeruginosa induces
soft rot, for example in
Arabidopsis thaliana (Thale cress) and
Lactuca sativa (lettuce). It is also pathogenic to invertebrate animals, including the nematode
Caenorhabditis elegans, the fruit fly
Drosophila, and the moth
Galleria mellonella. The associations of virulence factors are the same for plant and animal infections. In both insects and plants,
P. aeruginosa virulence is highly
quorum sensing (QS) dependent. Its QS is in turn highly dependent upon such genes as
acyl-homoserine-lactone synthase, and
lasI.
Quorum sensing P. aeruginosa is an opportunistic pathogen with the ability to coordinate gene expression in order to compete against other species for nutrients or colonization. Regulation of
gene expression can occur through cell-cell communication or
quorum sensing (QS) via the production of small molecules called
autoinducers that are released into the external environment. These signals, when reaching specific concentrations correlated with specific population cell densities, activate their respective regulators thus altering gene expression and coordinating behavior.
P. aeruginosa employs five interconnected QS systems
– las, rhl, pqs, iqs, and pch
– that each produce unique signaling molecules. The las and rhl systems are responsible for the activation of numerous QS-controlled genes, the pqs system is involved in quinolone signaling, and the iqs system plays an important role in intercellular communication. QS in
P. aeruginosa is organized in a hierarchical manner. At the top of the signaling hierarchy is the las system, since the las regulator initiates the QS regulatory system by activating the transcription of a number of other regulators, such as rhl. So, the las system defines a hierarchical QS cascade from the las to the rhl regulons. Detection of these molecules indicates
P. aeruginosa is growing as biofilm within the lungs of cystic fibrosis patients. The impact of QS and especially las systems on the pathogenicity of
P. aeruginosa is unclear, however. Studies have shown that lasR-deficient mutants are associated with more severe outcomes in cystic fibrosis patients and are found in up to 63% of chronically infected cystic fibrosis patients despite impaired QS activity. QS is known to control expression of a number of
virulence factors in a hierarchical manner, including the pigment pyocyanin. However, although the las system initiates the regulation of gene expression, its absence does not lead to loss of virulence factors. Recently, it has been demonstrated that the rhl system partially controls las-specific factors, such as proteolytic enzymes responsible for elastolytic and staphylolytic activities, but in a delayed manner. So, las is a direct and indirect regulator of QS-controlled genes.
Biofilms formation and cyclic di-GMP As in most Gram negative bacteria,
P. aeruginosa biofilm formation is regulated by one single molecule:
cyclic di-GMP. At low cyclic di-GMP concentration,
P. aeruginosa has a free-swimming mode of life. But when cyclic di-GMP levels increase,
P. aeruginosa start to establish sessile communities on surfaces. The intracellular concentration of cyclic di-GMP increases within seconds when
P. aeruginosa touches a surface (
e.g.: a rock, plastic, host tissues...). This activates the production of
adhesive pili, that serve as "anchors" to stabilize the attachment of
P. aeruginosa on the surface. At later stages, bacteria will start attaching irreversibly by producing a strongly adhesive matrix. At the same time, cyclic di-GMP represses the synthesis of the flagellar machinery, preventing
P. aeruginosa from swimming. When suppressed, the biofilms are less adherent and easier to treat. The
biofilm matrix of
P. aeruginosa is composed of nucleic acids, amino acids, carbohydrates, and various ions. It mechanically and chemically protects
P. aeruginosa from aggression by the immune system and some toxic compounds.
P. aeruginosa biofilm's matrix is composed of up to three types of sugar polymers (or "exopolysaccharides") named PSL, PEL, and alginate. Which exopolysaccharides are produced varies by strain. • The polysaccharide synthesis
operon and cyclic di-GMP form a positive feedback loop. This 15-gene operon is responsible for the cell-cell and cell-surface interactions required for cell communication. • PEL is a cationic exopolysaccharide that cross-links extracellular DNA in the
P. aeruginosa biofilm matrix. Upon certain cues or stresses,
P. aeruginosa revert the biofilm program and detach. Recent studies have shown that the dispersed cells from
P. aeruginosa biofilms have lower cyclic di-GMP levels and different physiologies from those of planktonic and biofilm cells, with unique population dynamics and motility. Such dispersed cells are found to be highly virulent against macrophages and
C. elegans, but highly sensitive towards iron stress, as compared with planktonic cells. ==Diagnosis==