|P. aeruginosa colony (right) on TSA|
Bacterium aeruginosum Schroeter 1872
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is citrate, catalase, and oxidase positive. 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, its 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 moist 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. On 29 April 2013, scientists in Rensselaer Polytechnic Institute, funded by NASA, reported that, during spaceflight inside the International Space Station, P. aeruginosa bacteria seem to adapt to the microgravity and the biofilms formed during spaceflight exhibited a column-and-canopy structure that has "not been observed on Earth".
- 1 Identification
- 2 Nomenclature
- 3 Genome
- 4 Cell-surface polysaccharides
- 5 Pathogenesis
- 6 Diagnosis
- 7 Treatment
- 8 See also
- 9 References
It is a gram-negative, aerobic, coccobacillus bacterium with unipolar motility. An opportunistic human pathogen, P. aeruginosa is also an opportunistic pathogen of plants. P. aeruginosa is the type species of the genus Pseudomonas (Migula).
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.
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. 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 lung mucus and alginate surrounding mucoid bacterial cells can limit the diffusion of oxygen.
- The word Pseudomonas means "false unit", from the Greek pseudo (Greek: ψευδο, false) and (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.
- 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.
The genome of P. aeruginosa is relatively large (6–7 Mb) and encodes around 6,000 (predicted) open reading frames, depending on the strain. The 5,021 genes are conserved across all five genomes analyzed, with at least 70% sequence identity. This set of genes is the P. aeruginosa core genome.
|genome size (bp)||6,905,121||6,222,097||6,264,404||6,537,648||6,492,423|
The G+C-rich P. 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 tRNALys or tRNAGly 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.
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.
|Infections||Details and common associations||High-risk groups|
|Pneumonia||Diffuse bronchopneumonia||Cystic fibrosis patients|
|Septic shock||Associated with a purple-black skin lesion ecthyma gangrenosum||Neutropenic patients|
|Urinary tract infection||Urinary tract catheterization|
|Gastrointestinal infection||Necrotising enterocolitis (NEC)||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, 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, research indicates salicylic acid can inhibit pyocyanin production. 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.
P. aeruginosa uses the virulence factor exotoxin A to inactivate eukaryotic elongation factor 2 via ADP-ribosylation in the host cell, much as the diphtheria toxin does. Without elongation factor 2, eukaryotic cells cannot synthesize proteins and necrotise. 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.
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 produced via a biosynthetic pathway. Pyocyanin, 1-Hydroxyphenazine, Phenazine-1-Carboxamide, 5-methylphenazine-1-carboxylic acid betaine, and Aeruginosin A. Two operons are involved in phenazine biosynthesis: phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2. These operons convert a chorismic acid to the phenazines mentioned above. Three key genes, phzH, phzM, and phzS convert phenazine-1-carboxylic acid to the phenazines mentioned above. Though phenazine biosynthesis is well studied, there are still questions as to the final structure of the brown phenazine pyomelanin.
Recently, a study found that when pyocyanin biosynthesis is inhibited that a decrease in P. aeruginosa pathogenicity is observed in vitro. This suggests that pyocyanin is most responsible for the initial colonization of P. aeruginosa in vivo.
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.
Plants and invertebrates
In higher plants, P. aeruginosa induces symptoms of 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.
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. Garlic experimentally blocks quorum sensing in P. aeruginosa.
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 quorum sensing 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.
There are many genes and factors that affect biofilm formation in P. aeruginosa. One of the main gene operons responsible for the initiation and maintaining the biofilm is the PSL operon. This 15 gene operon is responsible for the cell-cell and cell-surface interactions required for cell communication. It is also responsible for the sequestering of the Extracellular polymeric substance (EPS) matrix. This matrix is composed of nucleic acids, amino acids, carbohydrates and various ions. This matrix is one of the main resistance mechanisms in the biofilms of P. aeruginosa.
Cdi-GMP is a major contributor to biofilm adherent properties. This signalling molecule in high quantities makes super adherent biofilms. When supressed, the biofilms are less adherent and easier to treat. PSL (polysaccharide synthesis locus) and cdi-GMP form a negative feedback loop. PSL stimulates cdi-GMP production, while high cd-GMP turns on the operon and increases activity of the operon
Recently, scientists have been examining the possible genetic basis for P. aeruginosa resistance to antibiotics such as tobramycin. One locus identified as being an important genetic determinant of the resistance in this species is the ndvB locus, which encodes periplasmic glucans that may interact with antibiotics and cause them to become sequestered into the periplasm. These results suggest that there is, in fact, a genetic basis behind bacterial antibiotic resistance, rather than the biofilm simply acting as a diffusion barrier to the antibiotic.
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" or "fresh-tortilla" odor 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.
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.
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 (before administering first dose of antibiotic), and the choice of antibiotic used should be reviewed when the culture results are available.
Antibiotics that have activity against P. aeruginosa may include:
- aminoglycosides (gentamicin, amikacin, tobramycin, but not kanamycin)
- quinolones (ciprofloxacin, levofloxacin, but not moxifloxacin)
- cephalosporins (ceftazidime, cefepime, cefoperazone, cefpirome, ceftobiprole, but not cefuroxime, cefotaxime)
- antipseudomonal penicillins: carboxypenicillins (carbenicillin and ticarcillin), and ureidopenicillins (mezlocillin, azlocillin, and piperacillin). P. aeruginosa is intrinsically resistant to all other penicillins.
- carbapenems (meropenem, imipenem, doripenem, but not ertapenem)
- polymyxins (polymyxin B and colistin)
- 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.
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.) 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.
Antibiotic resistance and treatment
P. aeruginosahas immense potential to develop resistance against antibiotic as is evident from the fact that its genome contains the largest resistance island with more than 50 resistance genes. Mechanisms underlying antibiotic resistance have been found to include production of antibiotic-degrading or antibiotic-inactivating enzymes, outer membrane proteins to evict the antibiotics and mutations to change antibiotic targets. Presence of antibiotic-degrading enzymes such as extended-spectrum b-lactamases like PER-1, PER-2, VEB-1, AmpC cephalosporinases, carbapenemases like serine oxacillinases, metallo-b-lactamases, OXA-type carbapenemases, aminoglycoside-modifying enzymes, among others have been reported. P. aeruginosacan also modify the targets of antibiotic action like methylation of 16S rRNA to prevent aminoglycoside binding and modification of DNA topoisomerase to protect it from the action of quinolones. P. aeruginosahas also been reported to possess multidrug efflux pumps like AdeABC and AdeDE efflux systems that confer resistance against number of antibiotic classes. An important factor found to be associated with antibiotic resistance is the decrease in the virulence capabilities of the resistant strain. Such findings have been reported in the case of rifampicin-resistant and colistin resistant strains, in which decrease in infective ability, quorum sensing and motility have been documented. This seems to suggest that because of the lack of competition following antibiotic treatment, such strains can afford to compromise on their biological fitness because of the advantage conferred by the presence of resistance mechanisms. Owing to the increase in resistance among P. aeruginosa strains, the number of treatment options has become limited. Carbapenems, polymyxins and more recently tigecycline were considered to be the drugs of choice, but unfortunately, resistance against these drugs has also been reported. However, they are still being used in areas where resistance has not yet been reported. Use of blactamase inhibitors such as sulbactam is being advised in combination with antibiotics to enhance antimicrobial action even in the presence of certain level of resistance. Combination therapy after rigorous antimicrobial susceptibility testing has been found to be the best course of action in the treatment of multidrug-resistant P. aeruginosa. Some next-generation antibiotics that are reported as being active against P. aeruginosainclude doripenem, ceftobiprole and ceftaroline. However, these require more clinical trials for standardization. Therefore, research for the discovery of new antibiotics and drugs against P. aeruginosais very much needed.
Mutations in DNA gyrase are commonly associated with antibiotic resistance in P. aeruginosahas. These mutations, when combined with others, confer high resistance without hindering survival. Additionally, genes involved in cyclic-di-GMP signaling may contribute to resistance. When grown in vitro conditions designed to mimic a cystic fibrosis patient's lungs, these genes mutate repeatedly. 
Probiotic prophylaxis may prevent colonization and delay onset of pseudomonas infection in an ICU setting. Immunoprophylaxis against pseudomonas is being investigated. Avoiding hot tubs because Pseudomonas aeruginosa can survive in hot temperatures. Avoiding pools that may be poorly maintained and keep contact lens equipment and solutions from becoming contaminated. Washing your hands often can benefit as well with contact to many other pathogen infections. However there is no best way to prevent getting Pseudomonas aeruginosa the best treatment is to minimize exposure.
Phage therapy against P. aeruginosa has been investigated as a possible effective treatment, which can be combined with antibiotics, has no contraindications and minimal adverse effects. Phages are produced as sterile liquid, suitable for intake, applications etc. Phage therapy against ear infections caused by P. aeruginosa was reported in the journal Clinical Otolaryngology in August 2009.
|Wikimedia Commons has media related to Pseudomonas aeruginosa.|
- Balcht, Aldona; Smith, Raymond (1994). Pseudomonas aeruginosa: Infections and Treatment. Informa Health Care. pp. 83–84. ISBN 0-8247-9210-6.
- Itah, A.Y.; Essien, J.P. (2005). "Growth Profile and Hydrocarbonoclastic Potential of Microorganisms Isolated from Tarballs in the Bight of Bonny, Nigeria". World Journal of Microbiology and Biotechnology 21 (6–7): 1317–22. doi:10.1007/s11274-004-6694-z.
- AVI Biopharma (2007-01-18). "Antisense antibacterial method and compound". World Intellectual Property Organization. Retrieved 2008-10-18.
- Kim W et al. (29 April 2013). Beloin, Christophe, ed. "Spaceflight Promotes Biofilm Formation by Pseudomonas aeruginosa". Plos One 8 (4): e6237. doi:10.1371/journal.pone.0062437. Retrieved 5 July 2013.
- Ryan, KJ; Ray, CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.
- Iglewski BH (1996). "Pseudomonas". In Baron, S et al. Baron's Medical Microbiology (4th ed.). University of Texas Medical Branch. ISBN 0-9631172-1-1.
- Anzai Y, Kim H, Park JY, Wakabayashi H, Oyaizu H (Jul 2000). "Phylogenetic affiliation of the pseudomonads based on 16S rRNA sequence". Int J Syst Evol Microbiol 50 (4): 1563–89. doi:10.1099/00207713-50-4-1563. PMID 10939664.
- King EO, Ward MK, Raney DE (1954). "Two simple media for the demonstration of pyocyanin and fluorescein". J Lab Clin Med 44 (2): 301–7. PMID 13184240.
- Palmer KL, Brown SA, Whiteley M (2007). "Membrane-bound nitrate reductase is required for anaerobic growth in cystic fibrosis sputum". J. Bacteriol. 189 (12): 4449–55. doi:10.1128/JB.00162-07. PMC 1913347. PMID 17400735.
- Vander Wauven C, Piérard A, Kley-Raymann M, Haas D (1984). "Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway". J. Bacteriol. 160 (3): 928–34. PMC 215798. PMID 6438064.
- Hassett DJ (1996). "Anaerobic production of alginate by Pseudomonas aeruginosa: alginate restricts diffusion of oxygen". J. Bacteriol. 178 (24): 7322–5. PMC 178651. PMID 8955420.
- Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A, Meyer KC, Birrer P, Bellon G, Berger J, Weiss T, Botzenhart K, Yankaskas JR, Randell S, Boucher RC, Döring G (2002). "Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients". J. Clin. Invest. 109 (3): 317–325. doi:10.1172/JCI13870. PMC 150856. PMID 11827991.
- Cooper M, Tavankar GR, Williams HD (2003). "Regulation of expression of the cyanide-insensitive terminal oxidase in Pseudomonas aeruginosa". Microbiology 149 (Pt 5): 1275–84. doi:10.1099/mic.0.26017-0. PMID 12724389.
- Williams HD, Zlosnik JE, Ryall B (2007). "Oxygen, cyanide and energy generation in the cystic fibrosis pathogen Pseudomonas aeruginosa". Adv. Microb. Physiol. Advances in Microbial Physiology 52: 1–71. doi:10.1016/S0065-2911(06)52001-6. ISBN 9780120277520. PMID 17027370.
- Brown, RW (1956). Composition of Scientific Words. Smithsonian Institutional Press. ISBN 0-87474-286-2.
- Mathee K, Narasimhan G, Valdes C, Qiu X, Matewish JM, Koehrsen M, Rokas A, Yandava CN, Engels R, Zeng E, Olavarietta R, Doud M, Smith RS, Montgomery P, White JR, Godfrey PA, Kodira C, Birren B, Galagan JE, Lory S (2008). "Dynamics of Pseudomonas aeruginosa genome evolution". Proc. Natl. Acad. Sci. U.S.A. 105 (8): 3100–5. doi:10.1073/pnas.0711982105. PMC 2268591. PMID 18287045.
- Cornelis P (editor). (2008). Pseudomonas: Genomics and Molecular Biology (1st ed.). Caister Academic Press. ISBN 1-904455-19-0.
- Todar's Online Textbook of Bacteriology. Textbookofbacteriology.net (2004-06-04). Retrieved on 2011-10-09.
- Fine MJ, Smith MA, Carson CA, Mutha SS, Sankey SS, Weissfeld LA, Kapoor WN (1996). "Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis". JAMA 275 (2): 134–141. doi:10.1001/jama.275.2.134. PMID 8531309.
- Diekema DJ, Pfaller MA, Jones RN, Doern GV, Winokur PL, Gales AC, Sader HS, Kugler K, Beach M (1999). "Survey of bloodstream infections due to Gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997". Clin. Infect. Dis. 29 (3): 595–607. doi:10.1086/598640. PMID 10530454.
- Prithiviraj B, Bais HP, Weir T, Suresh B, Najarro EH, Dayakar BV, Schweizer HP, Vivanco JM (2005). "Down regulation of virulence factors of Pseudomonas aeruginosa by salicylic acid attenuates its virulence on Arabidopsis thaliana and Caenorhabditis elegans". Infect Immun 73 (9): 5319–28. doi:10.1128/IAI.73.9.5319-5328.2005. PMC 1231131. PMID 16113247.
- Dietrich, Price-Whelan, Petersen, Whiteley, & Newman, 2006
- Abu et al., 2013; Ho Sui et al., 2012; Mavrodi et al., 2001
- Ho Sui et al., 2012
- "Research could lead to new non-antibiotic drugs to counter hospital infections" (Press release). University of Chicago Medical Center. 2009-04-14. Retrieved 2010-01-18.
- Walker TS, Bais HP, Déziel E, Schweizer HP, Rahme LG, Fall R, Vivanco JM (2004). "Pseudomonas aeruginosa-plant root interactions. Pathogenicity, biofilm formation, and root exudation". Plant Physiol. 134 (1): 320–331. doi:10.1104/pp.103.027888. PMC 316311. PMID 14701912.
- Rahme LG, Stevens EJ, Wolfort SF, Shao J, Tompkins RG, Ausubel FM (1995). "Common virulence factors for bacterial pathogenicity in plants and animals". Science 268 (5219): 1899–1902. doi:10.1126/science.7604262. PMID 7604262.
- Rahme LG, Tan MW, Le L, Wong SM, Tompkins RG, Calderwood SB, Ausubel FM (1997). "Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors". Proc. Natl. Acad. Sci. U.S.A. 94 (24): 13245–50. doi:10.1073/pnas.94.24.13245. PMC 24294. PMID 9371831.
- Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM (1999). "Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model". Cell 96 (1): 47–56. doi:10.1016/S0092-8674(00)80958-7. PMID 9989496.
- Martínez C, Pons E, Prats G, León J (2004). "Salicylic acid regulates flowering time and links defence responses and reproductive development". Plant J. 37 (2): 209–17. doi:10.1046/j.1365-313X.2003.01954.x. PMID 14690505.
- D'Argenio DA, Gallagher LA, Berg CA, Manoil C (2001). "Drosophila as a model host for Pseudomonas aeruginosa infection". J. Bacteriol. 183 (4): 1466–71. doi:10.1128/JB.183.4.1466-1471.2001. PMC 95024. PMID 11157963.
- Miyata S, Casey M, Frank DW, Ausubel FM, Drenkard E (2003). "Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis". Infect. Immun. 71 (5): 2404–13. doi:10.1128/IAI.71.5.2404-2413.2003. PMC 153283. PMID 12704110.
- Rahme LG, Ausubel FM, Cao H, Drenkard E, Goumnerov BC, Lau GW, Mahajan-Miklos S, Plotnikova J, Tan MW, Tsongalis J, Walendziewicz CL, Tompkins RG (2000). "Plants and animals share functionally common bacterial virulence factors". Proc. Natl. Acad. Sci. U.S.A. 97 (16): 8815–21. doi:10.1073/pnas.97.16.8815. PMC 34017. PMID 10922040.
- Bjarnsholt T, Jensen PØ, Rasmussen TB, Christophersen L, Calum H, Hentzer M, Hougen HP, Rygaard J, Moser C, Eberl L, Høiby N, Givskov M (2005). "Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections". Microbiology 151 (4): 3873–80. doi:10.1099/mic.0.27955-0. PMID 16339933.
- Colvin et al., 2013
- Mah, T. F., Pitts, B., Pellock, B., Walker, G. C., Stewart, P. S., & O'Toole, G. A. (2003). A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature, 426(6964), 306-310.
- Hachem RY, Chemaly RF, Ahmar CA, Jiang Y, Boktour MR, Rjaili GA, Bodey GP, Raad II (2007). "Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients". Antimicrob. Agents Chemother. 51 (6): 1905–11. doi:10.1128/AAC.01015-06. PMC 1891378. PMID 17387153.
- Poole K (2004). "Efflux-mediated multiresistance in Gram-negative bacteria". Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 10 (1): 12–26. doi:10.1111/j.1469-0691.2004.00763.x. PMID 14706082.
- Wong, Alex; Rodrigue, Nicolas; Kassen, Rees (September 13, 2012). "Genomics of Adaptation during Experimental Evolution of the Opportunistic Pathogen Pseudomonas aeruginosa". PLoS Genetics 8 (9): e1002928. doi:10.1371/journal.pgen.1002928. PMC 3441735. Retrieved 24 March 2015.
- Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, De Champs C (2008). "Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in ICU-patients". Crit Care 12 (3): R69. doi:10.1186/cc6907. PMC 2481460. PMID 18489775.
- Döring G, Pier GB (2008). "Vaccines and immunotherapy against Pseudomonas aeruginosa". Vaccine 26 (8): 1011–24. doi:10.1016/j.vaccine.2007.12.007. PMID 18242792.
- Sulakvelidze A, Alavidze Z, Morris JG (2001). "Bacteriophage therapy". Antimicrobial Agents and Chemotherapy 45 (3): 649–659. doi:10.1128/AAC.45.3.649-659.2001. PMC 90351. PMID 11181338.
- Wright A, Hawkins CH, Anggård EE, Harper DR (2009). "A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy". Clinical Otolaryngology 34 (4): 349–357. doi:10.1111/j.1749-4486.2009.01973.x. PMID 19673983.