Gram-negative Pseudomonas aeruginosa bacteria (pink-red rods).

Pseudomonas aeruginosa is a Gram-negative, aerobic, rod-shaped bacterium with unipolar motility.^[1] An opportunistic human pathogen, P. aeruginosa is also an opportunistic pathogen of plants.^[2] P. aeruginosa is the type species of the genus Pseudomonas (Migula 1894).^[3]

P. aeruginosa ferments a variety of pigments, including pyocyanin (blue-green), fluorescein (yellow-green and fluorescent, now also known as pyoverdin), and pyorubin (red-brown). King, Ward, and Raney developed Pseudomonas Agar P (aka King A media) for enhancing pyocyanin and pyorubin production and Pseudomonas Agar F (aka King B media) for enhancing fluorescein production.^[4]

P. aeruginosa is often preliminarily identified by its pearlescent appearance and grape-like or tortilla-like odour in vitro. Definitive clinical identification of P. aeruginosa often includes identifying the production of both pyocyanin and fluorescein, as well as its ability to grow at 42°C. P. aeruginosa is capable of growth in diesel fuel and jet fuel, where it is known as a hydrocarbon-utilizing microorganism (or "HUM bug"), causing microbial corrosion.^[5] It creates dark gellish mats sometimes improperly called "algae" because of their appearance.

Although classified as an aerobic organism, P. aeruginosa is considered by many as a facultative anaerobe, as it is well adapted to proliferate in conditions of partial or total oxygen depletion. This organism can achieve anaerobic growth with nitrate as a terminal electron acceptor, and, in its absence, it is also able to ferment arginine by substrate-level phosphorylation. Adaptation to microaerobic or anaerobic environments is essential for certain lifestyles of P. aeruginosa, for example, during lung infection in cystic fibrosis patients, where thick layers of alginate surrounding bacterial mucoid cells can limit the diffusion of oxygen. ^{[6] [7] [8] [9] [10]}

Nomenclature

• The word Pseudomonas means false unit, from the Greek pseudo- (Greek: ?????, false) and monas (, from Greek: ?????, a single unit). The stem word mon was used early in the history of microbiology to refer to germs, e.g., Kingdom Monera.

• The species name aeruginosa is a Latin word meaning copper rust, as seen with the oxidized copper patina on the Statue of Liberty. This also describes the blue-green bacterial pigment seen in laboratory cultures of the species. This blue-green pigment is a combination of two metabolites of P. aeruginosa, pyocyanin (blue) and pyoverdine (yellow), which impart the blue-green characteristic color of cultures. Pyocyanin biosynthesis is regulated by quorum sensing as in the biofilms associated with colonization of the lungs in cystic fibrosis patients. Another assertion is that the word may be derived from the Greek prefix ae- meaning"old or aged, and the suffix ruginosa means wrinkled or bumpy.^[11]

• The derivations of pyocyanin and pyoverdine are of the Greek, with pyo-, meaning pus, cyanin, meaning blue, and verdine, meaning green. Pyoverdine in the absence of pyocyanin is a fluorescent-yellow color.

Genomic diversity

The G+C-rich Pseudomonas aeruginosa chromosome consists of a conserved core and a variable accessory part. The core genomes of P. aeruginosa strains are largely collinear, exhibit a low rate of sequence polymorphism, and contain few loci of high sequence diversity, notably the pyoverdine locus, the flagellar regulon, pilA, and the O-antigen biosynthesis locus. Variable segments are scattered throughout the genome, of which about one-third are immediately adjacent to tRNA or tmRNA genes. The three known hot spots of genomic diversity are caused by the integration of genomic islands of the pKLC102 / PAGI-2 family into tRNA^Lys or tRNA^Gly genes. The individual islands differ in their repertoire of metabolic genes, but share a set of syntenic genes that confer their horizontal spread to other clones and species. Colonization of atypical disease habitats predisposes to deletions, genome rearrangements, and accumulation of loss-of-function mutations in the P. aeruginosa chromosome. The P. aeruginosa population is characterized by a few dominant clones widespread in disease and environmental habitats. The genome is made up of clone-typical segments in core and accessory genome and of blocks in the core genome with unrestricted gene flow in the population.^[12]

Cell-surface polysaccharides

Cell-surface polysaccharides play diverse roles in the bacterial lifestyle. They serve as a barrier between the cell wall and the environment, mediate host-pathogen interactions, and form structural components of biofilms. These polysaccharides are synthesized from nucleotide-activated precursors, and, in most cases, all the enzymes necessary for biosynthesis, assembly, and transport of the completed polymer are encoded by genes organized in dedicated clusters within the genome of the organism. Lipopolysaccharide is one of the most important cell-surface polysaccharides, as it plays a key structural role in outer membrane integrity, as well as being an important mediator of host-pathogen interactions. The genetics for the biosynthesis of the so-called A-band (homopolymeric) and B-band (heteropolymeric) O antigens have been clearly defined, and much progress has been made toward understanding the biochemical pathways of their biosynthesis. The exopolysaccharide alginate is a linear copolymer of ?-1,4-linked D-mannuronic acid and L-glucuronic acid residues, and is responsible for the mucoid phenotype of late-stage cystic fibrosis disease. The pel and psl loci are two recently-discovered gene clusters that also encode exopolysaccharides found to be important for biofilm formation. Rhamnolipid is a biosurfactant whose production is tightly regulated at the transcriptional level, but the precise role that it plays in disease is not well understood at present. Protein glycosylation, particularly of pilin and flagellin, is a recent focus of research by several groups, and it has been shown to be important for adhesion and invasion during bacterial infection.^[12]

Pathogenesis

Pseudomonas co-infection of a toe-web (presented with a fungus)

P. aeruginosa uses the virulence factor exotoxin A to ADP-ribosylate eukaryotic elongation factor 2 in the host cell, much as the diphtheria toxin does. Without elongation factor 2, eukaryotic cells cannot synthesize proteins and necrose. The release of intracellular contents induces an immunologic response in immunocompetent patients.

With plants, P. aeruginosa induces symptoms of soft rot with Arabidopsis thaliana (Thale cress) and Letuca sativa (Lettuce)^[17][18]. It is a powerful pathogen with Arabidopsis^[19] and with some animals: Caenorhabditis elegans^[20][21], Drosophila^[22] and Galleria mellonella^[23]. The associations of virulence factors are the same for vegetal and animal infections^[17][24].

Quorum sensing

Regulation of gene expression can occur through cell-cell communication or quorum sensing (QS) via the production of small molecules called autoinducers. QS is known to control expression of a number of virulence factors. Another form of gene regulation that allows the bacteria to rapidly adapt to surrounding changes is through environmental signaling. Recent studies have discovered that anaerobiosis can significantly impact the major regulatory circuit of QS. This important link between QS and anaerobiosis has a significant impact on production of virulence factors of this organism.^[12]

Biofilms

The achievements of medical care in industrialised societies are markedly impaired due to chronic opportunistic infections that have become increasingly apparent in immunocompromised patients and the ageing population. Chronic infections remain a major challenge for the medical profession and are of great economic relevance because traditional antibiotic therapy is usually not sufficient to eradicate these infections. One major reason for persistence seems to be the capability of the bacteria to grow within biofilms that protect them from adverse environmental factors. Pseudomonas aeruginosa not only is an important opportunistic pathogen and causative agent of emerging nosocomial infections but also can be considered a model organism for the study of diverse bacterial mechanisms that contribute to bacterial persistence. In this context, the elucidation of the molecular mechanisms responsible for the switch from planctonic growth to a biofilm phenotype and the role of inter-bacterial communication in persistent disease should provide new insights in P. aeruginosa pathogenicity, contribute to a better clinical management of chronically infected patients, and should lead to the identification of new drug targets for the development of alternative anti-infective treatment strategies^[12].

Diagnosis

Production of pyocyanin, water-soluble green pigment of Pseudomonas aeruginosa. (left tube)

Treatment

P. aeruginosa is frequently isolated from non-sterile sites (mouth swabs, sputum, and so forth), and, under these circumstances, it often represents colonisation and not infection. The isolation of P. aeruginosa from non-sterile specimens should, therefore, be interpreted cautiously, and the advice of a microbiologist or infectious diseases physician should be sought prior to starting treatment. Often no treatment is needed.

When P. aeruginosa is isolated from a sterile site (blood, bone, deep collections), it should be taken seriously, and almost always requires treatment.

P. aeruginosa is naturally resistant to a large range of antibiotics and may demonstrate additional resistance after unsuccessful treatment, particularly through modification of a porin. It should usually be possible to guide treatment according to laboratory sensitivities, rather than choosing an antibiotic empirically. If antibiotics are started empirically, then every effort should be made to obtain cultures, and the choice of antibiotic used should be reviewed when the culture results are available.

Antibiotics that have activity against P. aeruginosa include:

• aminoglycosides (gentamicin, amikacin, tobramycin);
• quinolones (ciprofloxacin and levofloxacin but not moxifloxacin)
• cephalosporins (ceftazidime, cefepime, cefpirome, but not cefuroxime, ceftriaxone, cefotaxime)
• ureidopenicillins (piperacillin, ticarcillin: P. aeruginosa is intrinsically resistant to all other penicillins)
• carbapenems (meropenem, imipenem, but not ertapenem)
• polymyxins (polymyxin B and colistin)^[25]
• monobactams (aztreonam)

These antibiotics must all be given by injection, with the exception of fluoroquinolones and of aerosolized tobramycin. For this reason, in some hospitals, fluoroquinolone use is severely restricted in order to avoid the development of resistant strains of P. aeruginosa. In the rare occasions where infection is superficial and limited (for example, ear infections or nail infections), topical gentamicin or colistin may be used.

Antibiotic resistance

Pseudomonas aeruginosa is a highly relevant opportunistic pathogen. One of the most worrisome characteristics of P. aeruginosa is its low antibiotic susceptibility. This low susceptibility is attributable to a concerted action of multidrug efflux pumps with chromosomally-encoded antibiotic resistance genes and the low permeability of the bacterial cellular envelopes. In addition to this intrinsic resistance, P. aeruginosa easily develops acquired resistance either by mutation in chromosomally-encoded genes or by the horizontal gene transfer of antibiotic resistance determinants. Development of multidrug resistance by P. aeruginosa isolates requires several different genetic events that include acquisition of different mutations and/or horizontal transfer of antibiotic resistance genes. Hypermutation favours the selection of mutation-driven antibiotic resistance in P. aeruginosa strains producing chronic infections, whereas the clustering of several different antibiotic resistance genes in integrons favors the concerted acquisition of antibiotic resistance determinants. Some recent studies have shown that phenotypic resistance associated to biofilm formation or to the emergence of small-colony variants may be important in the response of P. aeruginosa populations to antibiotics treatment.^[12]

Prevention

Medical-Grade honey (i.e., containing Unique Manuka Factor) may reduce colonization of many pathogens including pseudomonas aeruginosa.^[26] Probiotic prophylaxis may prevent colonization and delay onset of pseudomonas infection in an ICU setting.^[27] Immunoprophylaxis against pseudomonas is being investigated. ^[28]

References

See also

• Bacteriological water analysis
• Contamination control
• Nosocomial infection

External links

• www.pseudomonas.com, the Pseudomonas genome database
• Migula's Systematic Bacteriology
• Spotlight on Pseudomonas

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