Pseudomonas aeruginosa
From Wikipedia, the free encyclopedia
Pseudomonas aeruginosa is a common
bacterium that can cause
disease in animals, including humans. It is found in soil, water,
skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in
hypoxic atmospheres, and has, thus, colonized many natural and artificial environments. It uses a wide range of organic material for food; in animals, the versatility enables the organism to infect damaged tissues or those with reduced immunity. The symptoms of such infections are generalized
inflammation and
sepsis. If such colonizations occur in critical body organs, such as the
lungs, the
urinary tract, and
kidneys, the results can be fatal. Because it thrives on most surfaces, this bacterium is also found on and in
medical equipment, including
catheters, causing cross-
infections in
hospitals and
clinics. It is implicated in
hot-tub rash. It is also able to decompose hydrocarbons and has been used to break down
tarballs and oil from
oil spills.
Identification
It is a
Gram-negative,
aerobic, rod-shaped
bacterium with
unipolar motility.
[4] An
opportunistic human pathogen,
P. aeruginosa is also an opportunistic pathogen of plants.
[5] P. aeruginosa is the
type species of the genus
Pseudomonas (Migula).
[6]
P. aeruginosa secretes a variety of pigments, including
pyocyanin (blue-green),
pyoverdine (yellow-green and
fluorescent), and pyorubin (red-brown). King, Ward, and Raney developed
Pseudomonas Agar P (King A medium) for enhancing pyocyanin and pyorubin production, and
Pseudomonas Agar F (King B medium) for enhancing fluorescein production.
[7]
Pseudomonas aeruginosa fluorescence under UV illumination
P. aeruginosa is often preliminarily identified by its
pearlescent appearance and grape-like or tortilla-like odor
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 and
jet fuel, where it is known as a
hydrocarbon-using
microorganism (or "HUM bug"), causing
microbial corrosion.
[3] It creates dark, gellish mats sometimes improperly called "
algae" because of their appearance.
[citation needed]
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.
[8][9] 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 lung
mucus and
alginate surrounding mucoid bacterial cells can limit the diffusion of oxygen.
[10][11][12][13]
Nomenclature
- The word Pseudomonas means "false unit", from the Greek pseudo (Greek: ψευδο, false) and monas (Latin: monas, from Greek: μονος, 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 verdigris ("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 (green), 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.[14]
- 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.
Gram-stained
Pseudomonas aeruginosa bacteria (pink-red rods)
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, the most notable ones being 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.
[15]
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 β-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, which also encode exopolysaccharides found to be important for biofilm formation. A
rhamnolipid is a biosurfactant whose production is tightly regulated at the
transcriptional level, but the precise role it plays in disease is not well understood at present. Protein
glycosylation, in particular 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.
[15]
Pathogenesis
Phagocytosis of
P. aeruginosa by neutrophil in patient with bloodstream infection (Gram stain)
An
opportunistic,
nosocomial pathogen of
immunocompromised individuals,
P. aeruginosa typically infects the pulmonary tract,
urinary tract,
burns,
wounds, and also causes other
blood infections.
[16]
| Infections | Details and common associations | High-risk groups |
|---|
| Pneumonia | Diffuse bronchopneumonia | Cystic fibrosis patients |
| Septic shock | Associated with a purple-black skin lesion ecthyma gangerenosum | Neutropenic patients |
| Urinary tract infection | Urinary tract catheterization | |
| Gastrointestinal infection | Necrotising enterocolitis (NEC) | NEC, especially in premature infants and neutropenic cancer patients |
| Skin and soft tissue infections | Hemorrhage and necrosis | Burns victims and patients with wound 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, in rare circumstances, cause
community-acquired pneumonias,
[17] as well as
ventilator-associated pneumonias, being one of the most common agents isolated in several studies.
[18] Pyocyanin is a
virulence factor of the bacteria and has been known to cause death in
C. elegans by
oxidative stress. However, research indicates
salicylic acid can inhibit pyocyanin production.
[19] One in ten hospital-acquired infections are from
Pseudomonas.
Cystic fibrosis patients are also predisposed to
P. aeruginosa infection of the lungs.
P. aeruginosa may also be a common cause of "hot-tub rash" (
dermatitis), caused by lack of proper, periodic attention to water quality. The most common cause of burn infections is
P. aeruginosa.
Pseudomonas is also a common cause of postoperative infection in
radial keratotomy surgery patients. The organism is also associated with the skin lesion
ecthyma gangrenosum.
P. aeruginosa is frequently associated with
osteomyelitis involving puncture wounds of the foot, believed to result from direct inoculation with
P. aeruginosa via the foam padding found in tennis shoes, with diabetic patients at a higher risk.
Toxins
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. In addition
P. aeruginosa uses an exoenzyme, ExoU, which degrades the plasma membrane of eukaryotic cells, leading to lysis.
Triggers
With low
phosphate levels,
P. aeruginosa has been found to activate from benign symbiont to express lethal toxins inside the intestinal tract and severely damage or kill the host, which can be mitigated by providing excess phosphate instead of antibiotics.
[20]
Plants and invertebrates
In higher plants,
P. aeruginosa induces symptoms of soft rot, for example in
Arabidopsis thaliana (Thale cress)
[21] and
Lactuca sativa (lettuce).
[22][23] It is also pathogenic to invertebrate animals, including the nematode
Caenorhabditis elegans,
[24][25] the fruit fly
Drosophila[26] and the moth
Galleria mellonella.[27] The associations of virulence factors are the same for plant and animal infections.
[22][28]
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
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.
[15] Garlic experimentally blocks quorum sensing in
P. aeruginosa.
[29]
Biofilms and treatment resistance
Biofilms of
P. aeruginosa can cause chronic
opportunistic infections, which are a serious problem for medical care in industrialized societies, especially for immunocompromised patients and the elderly. They often cannot be treated effectively with traditional
antibiotic therapy. Biofilms seem to protect these bacteria from adverse environmental factors.
P. aeruginosa can cause
nosocomial infections and is considered a
model organism for the study of antibiotic-resistant bacteria. Researchers consider it important to learn more about the molecular mechanisms that cause the switch from
planktonic growth to a biofilm phenotype and about the role of
interbacterial communication in treatment-resistant bacteria such as
P. aeruginosa. This should contribute to better clinical management of chronically infected patients, and should lead to the development of new drugs.
[15]
Diagnosis
Production of pyocyanin, water-soluble blue pigment of
Pseudomonas aeruginosa (left tube)
Depending on the nature of
infection, an appropriate specimen is collected and sent to a
bacteriology laboratory for identification. As with most bacteriological specimens, a
Gram stain is performed, which may show Gram-negative rods and/or
white blood cells.
P. aeruginosa produces colonies with a characteristic 'grape-like' odour on bacteriological media. In mixed cultures, it can be isolated as clear colonies on
MacConkey agar (as it does not ferment lactose) which will test positive for
oxidase. Confirmatory tests include production of the blue-green pigment
pyocyanin on
cetrimide agar and growth at 42°C. A
TSI slant is often used to distinguish nonfermenting
Pseudomonas species from enteric pathogens in faecal specimens.
Treatment
P. aeruginosa is frequently isolated from nonsterile sites (mouth swabs,
sputum, etc.), and, under these circumstances, it often represents colonization and not infection. The isolation of
P. aeruginosa from nonsterile specimens should, therefore, be interpreted cautiously, and the advice of a
microbiologist or infectious diseases physician/pharmacist 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.
[citation needed]
P. aeruginosa is naturally
resistant to a large range of antibiotics and may demonstrate additional resistance after unsuccessful treatment, in particular, 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.
Phage therapy against
P. aeruginosa remains one of the most effective treatments, which can be combined with antibiotics, has no contraindications and minimal adverse effects. Phages are produced as sterile liquid, suitable for intake, applications etc.
[30] Phage therapy against ear infections caused by
P. aeruginosa was reported in the journal
Clinical Otolaryngology in August 2009
[31]
Antibiotics that have activity against
P. aeruginosa may include:
- aminoglycosides (gentamicin, amikacin, tobramycin)
- quinolones (ciprofloxacin, levofloxacin, but not moxifloxacin)
- cephalosporins (ceftazidime, cefepime, cefoperazone, cefpirome, but not cefuroxime, ceftriaxone, cefotaxime)
- antipseudomonal penicillins: ureidopenicillins and carboxypenicillins (piperacillin, ticarcillin: P. aeruginosa is intrinsically resistant to all other penicillins)
- carbapenems (meropenem, imipenem, doripenem, but not ertapenem)
- polymyxins (polymyxin B and colistin)[32]
- monobactams (aztreonam)
These antibiotics must all be given by
injection, with the exceptions of fluoroquinolones, aerosolized tobramycin and aerosolized aztreonam. For this reason, in some hospitals, fluoroquinolone use is severely restricted 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
One of the most worrisome characteristics of
P. aeruginosa is its low
antibiotic susceptibility, which is attributable to a concerted action of multidrug
efflux pumps with chromosomally encoded
antibiotic resistance genes (e.g.,
mexAB,
mexXY etc.
[33]) 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, including 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 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.
[15]
Phosphate trigger
Phosphate has been implicated in pathogenesis of
P. aeruginosa, which is normally benign. Phosphate is required by the bacteria for normal functioning, and has been shown in experiments on two very different organisms to turn on its host.
[20]
Prevention
Probiotic prophylaxis may prevent colonization and delay onset of pseudomonas infection in an ICU setting.
[34] Immunoprophylaxis against pseudomonas is being investigated
*
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