| Pseudomonas aeruginosa | |
|---|---|
 | |
| P. aeruginosa colonies onblood agar | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Pseudomonadati |
| Phylum: | Pseudomonadota |
| Class: | Gammaproteobacteria |
| Order: | Pseudomonadales |
| Family: | Pseudomonadaceae |
| Genus: | Pseudomonas |
| Species: | P. aeruginosa |
| Binomial name | |
| Pseudomonas aeruginosa (Schröter 1872) Migula 1900 | |
| Synonyms | |
| |
Pseudomonas aeruginosa is a commonencapsulated,Gram-negative,aerobic–facultatively anaerobic,rod-shapedbacterium that can causedisease in plants and animals, including humans.[1][2] Aspecies of considerable medical importance,P. aeruginosa is amultidrug resistant pathogen recognized for its ubiquity, itsintrinsically advancedantibiotic resistance mechanisms, and its association with serious illnesses –hospital-acquired infections such asventilator-associated pneumonia and varioussepsissyndromes.P. aeruginosa is able to selectively inhibit various antibiotics from penetrating its outer membrane – and has high resistance to several antibiotics. According to theWorld Health OrganizationP. aeruginosa poses one of the greatest threats to humans in terms of antibiotic resistance.[3]
The organism is consideredopportunistic insofar as serious infection often occurs during existingdiseases or conditions – most notablycystic fibrosis and traumatic burns. It generally affects theimmunocompromised but can also infect theimmunocompetent as inhot tub folliculitis. Treatment ofP. aeruginosa infections can be difficult due to its natural resistance to antibiotics. When more advanced antibiotic drug regimens are neededadverse effects may result.
It iscitrate-,catalase-, andoxidase-positive. It is found in soil, water,skin flora, and most human-made environments throughout the world. As afacultative anaerobe,P. aeruginosa thrives in diverse habitats. 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 generalizedinflammation andsepsis. If such colonizations occur in critical body organs, such as thelungs, theurinary tract, andkidneys, the results can be fatal.[4]
Because it thrives on moist surfaces, this bacterium is also found on and in soap andmedical equipment, includingcatheters, causing cross-infections inhospitals andclinics.[5] It is also able to decompose hydrocarbons and has been used to break downtarballs and oil fromoil spills.[6]P. aeruginosa is not extremelyvirulent in comparison with other major species ofpathogenic bacteria such asGram-positiveStaphylococcus aureus andStreptococcus pyogenes – thoughP. aeruginosa is capable of extensive colonization, and can aggregate into enduringbiofilms.[7] Its genome includes numerous genes fortranscriptional regulation and antibiotic resistance, such as efflux systems and beta-lactamases, which contribute to its adaptability and pathogenicity in human hosts.[8][9]P. aeruginosa produces a characteristic sweet, grape-like odor due to its synthesis of2-aminoacetophenone.[10]
The wordPseudomonas means "false unit", from the Greekpseudēs (Greek: ψευδής, false) and (Latin:monas, fromGreek: μονάς, a single unit). The stem wordmon was used early in the history ofmicrobiology to refer tomicroorganisms andgerms, e.g., kingdomMonera.[11]
The species nameaeruginosa is a Latin adjective form derived from the nounaerūgō meaningverdigris ("copper rust"),[12] here applied in reference to the blue-green (verdigris-like) colour seen in laboratory cultures of the species. This blue-green pigment is a combination of twosecondary metabolites ofP. aeruginosa,pyocyanin (blue) andpyoverdine (green), which impart the blue-green characteristic color of cultures.[11]
Thegenome ofPseudomonas aeruginosa consists of a relatively large circular chromosome (5.5–6.8 Mb) that carries between 5,500 and 6,000open reading frames, and sometimesplasmids of various sizes depending on thestrain.[13] Comparison of 389 genomes from differentP. aeruginosa strains showed that just 17.5% is shared. This part of the genome is theP. aeruginosa core genome.[14]
| strain: | VRFPA04 | C3719 | PAO1 | PA14 | PACS2 |
|---|---|---|---|---|---|
| Chromosome size (bp) | 6,818,030 | 6,222,097 | 6,264,404 | 6,537,648 | 6,492,423 |
| ORFs | 5,939 | 5,578 | 5,571 | 5,905 | 5,676 |
A comparative genomic study (in 2020) analyzed 494 complete genomes from thePseudomonas genus, of which 189 wereP. aeruginosa strains.[15] The study observed that their protein count andGC content ranged between 5500 and 7352 (average: 6192) and between 65.6 and 66.9% (average: 66.1%), respectively.[15] This comparative analysis further identified 1811 aeruginosa-core proteins, which accounts for more than 30% of the proteome. The higher percentage of aeruginosa-core proteins in this latter analysis could partly be attributed to the use of complete genomes. AlthoughP. aeruginosa is a very well-definedmonophyletic species, phylogenomically and in terms of ANIm values, it is surprisingly diverse in terms of protein content, thus revealing a very dynamic accessory proteome, in accordance with several analyses.[15][16][17][18] It appears that, on average, industrial strains have the largest genomes, followed by environmental strains, and then clinical isolates.[15][19] The same comparative study (494Pseudomonas strains, of which 189 areP. aeruginosa) identified that 41 of the 1811P. aeruginosa core proteins were present only in this species and not in any other member of the genus, with 26 (of the 41) being annotated as hypothetical. Furthermore, another 19 orthologous protein groups are present in at least 188/189P. aeruginosa strains and absent in all the other strains of the genus.[citation needed]
The population ofP. aeruginosa can be classified in three main lineages, genetically characterised by the model strains PAO1, PA14, and the more divergent PA7.[20]
WhileP. aeruginosa is generally thought of as an opportunistic pathogen, several widespread clones appear to have become more specialised pathogens, particularly incystic fibrosis patients, including the Liverpool epidemic strain (LES) which is found mainly in the UK,[21] DK2 in Denmark,[22] and AUST-02 in Australia (also previously known as AES-2 and P2).[23] There is also a clone that is frequently found infecting the reproductive tracts of horses.[24][25]
P. aeruginosa is afacultative anaerobe, as it is well adapted to proliferate in conditions of partial or total oxygen depletion. This organism can achieveanaerobic growth withnitrate ornitrite as aterminal electron acceptor. When oxygen, nitrate, and nitrite are absent, it is able to fermentarginine andpyruvate bysubstrate-level phosphorylation.[26] Additionally, phenazines produced byP. aeruginosa can act as electron shuttles to facilitate survival of cells at depth in biofilms.[27] Adaptation tomicroaerobic or anaerobic environments is essential for certain lifestyles ofP. aeruginosa, for example, during lung infection incystic fibrosis andprimary ciliary dyskinesia, where thick layers of lungmucus and bacterially-producedalginate surrounding mucoid bacterial cells can limit the diffusion of oxygen.P. aeruginosa growth within the human body can be asymptomatic until the bacteria form a biofilm, which overwhelms the immune system. These biofilms are found in the lungs of people with cystic fibrosis and primary ciliary dyskinesia, and can prove fatal.[28][29][30][31][32][33][excessive citations]
P. aeruginosa relies oniron as anutrient source to grow. However, iron is not easily accessible because it is not commonly found in the environment. Iron is usually found in a largely insolubleferric form.[34] Furthermore, excessively high levels of iron can be toxic toP. aeruginosa. To overcome this and regulate proper intake of iron,P. aeruginosa usessiderophores, which are secreted molecules that bind and transport iron.[35] These iron-siderophore complexes, however, are not specific. The bacterium that produced the siderophores does not necessarily receive the direct benefit of iron intake. Rather, all members of the cellular population are equally likely to access the iron-siderophore complexes. Members of the cellular population that can efficiently produce these siderophores are commonly referred to as cooperators; members that produce little to no siderophores are often referred to as cheaters. Research has shown when cooperators and cheaters are grown together, cooperators have a decrease in fitness, while cheaters have an increase in fitness.[36] The magnitude of change in fitness increases with increasing iron limitation.[37] With an increase in fitness, the cheaters can outcompete the cooperators; this leads to an overall decrease in fitness of the group, due to lack of sufficient siderophore production. These observations suggest that having a mix of cooperators and cheaters can reduce the virulent nature ofP. aeruginosa.[36]
LigDs form a subfamily of theDNA ligases. These all have a LigDom/ligase domain, but many bacterial LigDs also have separatepolymerase domains/PolDoms andnuclease domains/NucDoms. InP. aeruginosa's case the nuclease domains areN-terminus, and the polymerase domains areC-terminus, extensions of the single central ligase domain.[38]
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Frequently acting as anopportunistic,nosocomial pathogen ofimmunocompromised individuals, but capable of infecting the immunocompetent,P. aeruginosa typically infects the airway,urinary tract,burns, andwounds, and also causes otherblood infections.[39][40]
| Infections | Details and common associations | High-risk groups |
|---|---|---|
| Pneumonia | Diffuse bronchopneumonia | Cystic fibrosis, non-CFbronchiectasis patients |
| Septic shock | Associated with a purple-black skin lesionecthyma gangrenosum | Neutropenic patients |
| Urinary tract infection | Urinary tract catheterization | |
| Gastrointestinal infection | Necrotising enterocolitis | Premature infants and neutropenic cancer patients |
| Skin and soft tissue infections | Hemorrhage and necrosis | People withburns or wound infections |
It is the most common cause of infections of burn injuries and of theouter 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.[41]Pseudomonas can, in rare circumstances, causecommunity-acquired pneumonias,[42] as well asventilator-associated pneumonias, being one of the most common agents isolated in several studies.[43]Pyocyanin is avirulence factor of the bacteria and has been known to cause death inC. elegans byoxidative stress. However,salicylic acid can inhibit pyocyanin production.[44] One in ten hospital-acquired infections is fromPseudomonas[citation needed].Cystic fibrosis patients are also predisposed toP. aeruginosa infection of the lungs due to a functional loss in chloride ion movement across cell membranes as a result of amutation.[45]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.[41]Pseudomonas is also a common cause of postoperative infection inradial keratotomy surgery patients. The organism is also associated with the skin lesionecthyma gangrenosum.P. aeruginosa is frequently associated withosteomyelitis involving puncture wounds of the foot, believed to result from direct inoculation withP. aeruginosa via the foam padding found in tennis shoes, with diabetic patients at a higher risk.
A comparative genomic analysis of 494 completePseudomonas genomes, including 189 completeP. aeruginosa genomes, identified several proteins that are shared by the vast majority ofP. aeruginosa strains, but are not observed in other analyzedPseudomonas genomes.[15] TheseP. aeruginosa-specific core genes, such ascntL, cntM, plcB, acp1, mucE, srfA, tse1, tsi2, tse3, andesrC are known to play an important role in this species' pathogenicity.[15]
P. aeruginosa uses thevirulence factorexotoxin A to inactivateeukaryotic elongation factor 2 viaADP-ribosylation in the host cell, much as thediphtheria toxin does. Without elongation factor 2,eukaryotic cells cannot synthesizeproteins and necrotise. The release of intracellular contents induces animmunologic response inimmunocompetent patients.In additionP. aeruginosa uses an exoenzyme, ExoU, which degrades the plasma membrane of eukaryotic cells, leading tolysis. Increasingly, it is becoming recognized that the iron-acquiringsiderophore,pyoverdine, also functions as a toxin by removingiron frommitochondria, inflicting damage on this organelle.[46][47] 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.[48]
Phenazines are redox-active pigments produced byP. aeruginosa. These pigments are involved inquorum sensing,virulence, and iron acquisition.[49]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 andphzA2B2C2D2E2F2G2.[50][51][52] The enzymes encoded by these operons convertchorismic acid to PCA. The products of three key genes,phzH,phzM, andphzS 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.[citation needed]
When pyocyanin biosynthesis is inhibited, a decrease inP. aeruginosa pathogenicity is observedin vitro. This suggests that pyocyanin is mostly responsible for the initial colonization ofP. aeruginosain vivo.[52]
With lowphosphate 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.[53]
In higher plants,P. aeruginosa inducessoft rot, for example inArabidopsis thaliana (Thale cress)[54] andLactuca sativa (lettuce).[55][56] It is also pathogenic to invertebrate animals, including the nematodeCaenorhabditis elegans,[57][58] the fruit flyDrosophila,[59] and the mothGalleria mellonella.[60] The associations of virulence factors are the same for plant and animal infections.[55][61] In both insects and plants,P. aeruginosavirulence is highlyquorum sensing (QS) dependent.[62] Its QS is in turn highly dependent upon such genes asacyl-homoserine-lactone synthase, andlasI.[63]
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 ofgene expression can occur through cell-cell communication orquorum sensing (QS) via the production of small molecules calledautoinducers 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.[64] 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.[65] QS inP. 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.[66] Detection of these molecules indicatesP. aeruginosa is growing as biofilm within the lungs of cystic fibrosis patients.[67] The impact of QS and especially las systems on the pathogenicity ofP. aeruginosa is unclear, however. Studies have shown that lasR-deficient mutants are associated with more severe outcomes in cystic fibrosis patients[68] and are found in up to 63% of chronically infected cystic fibrosis patients despite impaired QS activity.[69]
QS is known to control expression of a number ofvirulence 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.[65] Another form ofgene regulation that allows the bacteria to rapidly adapt to surrounding changes is through environmental signaling. Recent studies have discoveredanaerobiosis 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.[70]Garlic experimentally blocks quorum sensing inP. aeruginosa.[71]
As in most Gram negative bacteria,P. aeruginosabiofilm 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 whenP. aeruginosa touches a surface (e.g.: a rock, plastic, host tissues...).[72] This activates the production ofadhesive pili, that serve as "anchors" to stabilize the attachment ofP. 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, preventingP. aeruginosa from swimming. When suppressed, the biofilms are less adherent and easier to treat.Thebiofilm matrix ofP. aeruginosa is composed of nucleic acids, amino acids, carbohydrates, and various ions. It mechanically and chemically protectsP. aeruginosa from aggression by the immune system and some toxic compounds.[73]P. aeruginosa biofilm's matrix is composed of up to three types of sugar polymers (or "exopolysaccharides") named PSL, PEL, and alginate.[74] Which exopolysaccharides are produced varies by strain.[75]
Upon certain cues or stresses,P. aeruginosa revert the biofilm program and detach. Recent studies have shown that the dispersed cells fromP. aeruginosa biofilms have lower cyclic di-GMP levels and different physiologies from those of planktonic and biofilm cells,[77][78] with unique population dynamics and motility.[79] Such dispersed cells are found to be highly virulent against macrophages andC. elegans, but highly sensitive towards iron stress, as compared with planktonic cells.[77]
Biofilms ofP. aeruginosa can cause chronicopportunistic 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 traditionalantibiotic therapy. Biofilms serve to protect these bacteria from adverse environmental factors, including host immune system components in addition to antibiotics.P. aeruginosa can cause nosocomial infections and is considered amodel 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 QS in treatment-resistant bacteria such asP. aeruginosa. This should contribute to better clinical management of chronically infected patients, and should lead to the development of new drugs.[70]
Scientists have been examining the possible genetic basis forP. aeruginosa resistance to antibiotics such astobramycin. Onelocus identified as being an important genetic determinant of the resistance in this species isndvB, which encodesperiplasmicglucans that may interact with antibiotics and cause them to become sequestered into the periplasm. These results suggest a genetic basis exists behind bacterial antibiotic resistance, rather than the biofilm simply acting as a diffusion barrier to the antibiotic.[80]
Depending on the nature of infection, an appropriate specimen is collected and sent to abacteriology laboratory for identification. As with most bacteriological specimens, aGram stain is performed, which may show Gram-negative rods and/orwhite 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 onMacConkey agar (as it does not fermentlactose) which will test positive foroxidase. Confirmatory tests include production of the blue-green pigment pyocyanin oncetrimide agar and growth at 42 °C. ATSI slant is often used to distinguish nonfermentingPseudomonas species from enteric pathogens in faecal specimens.[citation needed]
WhenP. aeruginosa is isolated from a normally sterile site (blood, bone, deep collections), it is generally considered dangerous, and almost always requires treatment.[81][82] However,P. aeruginosa is frequently isolated from nonsterile sites (mouth swabs,sputum, etc.), and, under these circumstances, it may represent colonization and not infection. The isolation ofP. aeruginosa from nonsterile specimens should, therefore, be interpreted cautiously, and the advice of amicrobiologist or infectious diseases physician/pharmacist should be sought prior to starting treatment. Often, no treatment is needed.[citation needed]
Morphological, physiological, and biochemical characteristics ofPseudomonas aeruginosa are shown in the Table below.
| Test type | Test | Characteristics |
|---|---|---|
| Colony characters | Size | Large |
| Type | Smooth | |
| Color | ||
| Shape | Flat | |
| Morphological characters | Shape | Rod |
| Physiological characters | Motility | + |
| Growth at 6.5% NaCl | - | |
| Biochemical characters | Gram staining | - |
| Oxidase | + | |
| Catalase | + | |
| Oxidative-Fermentative | ||
| Motility | + | |
| Methyl Red | - | |
| Voges-Proskauer | - | |
| Indole | - | |
| H2S Production | - | |
| Urease | - | |
| Nitrate reductase | + | |
| β-Galactosidase | ||
| Phenylalanine Deaminase | - | |
| DNAse | - | |
| Lipase | + | |
| Lysine Decarboxylase | - | |
| Pigment | + (bluish green pigmentation) | |
| Hemolysis | Beta/variable | |
| Hydrolysis of | Gelatin | + |
| Casein | ||
| Utilization of | Glycerol | + |
| Galactose | - | |
| D-Glucose | + | |
| D-Fructose | + | |
| D-Mannose | - | |
| Mannitol | + | |
| Citrate | + | |
| Maltose | - | |
| Sucrose | - | |
| Lactose | - |
Note: + = Positive, - =Negative
P. aeruginosa is a Gram-negative,aerobic (and at timesfacultatively anaerobic), rod-shaped bacterium withunipolar motility.[83] It has been identified as anopportunistic pathogen of both humans and plants.[84]P. aeruginosa is thetype species of the genusPseudomonas.[85]
Identification ofP. aeruginosa can be complicated by the fact individual isolates often lack motility. The colony morphology itself also displays several varieties. The main two types are large, smooth, with a flat edge and elevated center and small, rough, and convex.[86] A third type, mucoid, can also be found. The large colony can typically be found in clinal settings while the small is found in nature.[86] The third, however, is present in biological settings and has been found in respiratory and in the urinary tract.[86] Furthermore, mutations in the gene lasR drastically alter colony morphology and typically lead to failure to hydrolyze gelatin or hemolyze.[citation needed]
In certain conditions,P. aeruginosa can secrete a variety of pigments, includingpyocyanin (blue),pyoverdine (yellow andfluorescent), pyorubin (red), and pyomelanin (brown). These can be used to identify the organism.[87]
Clinical identification ofP. aeruginosa may include identifying the production of both pyocyanin and fluorescein, as well as its ability to grow at 42 °C.P. aeruginosa is capable of growth indiesel andjet fuels, where it is known as ahydrocarbon-usingmicroorganism, causingmicrobial corrosion.[88] It creates dark, gellish mats sometimes improperly called "algae" because of their appearance.[citation needed]
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ManyP. aeruginosa isolates areresistant to a large range of antibiotics and may demonstrate additional resistance after unsuccessful treatment. It should usually be possible to guide treatment according to laboratory sensitivities, rather than choosing an antibioticempirically. If antibiotics are started empirically, then every effort should be made to obtain cultures (before administering the first dose of antibiotic), and the choice of antibiotic used should be reviewed when the culture results are available.
Due to widespread resistance to many common first-line antibiotics,carbapenems,polymyxins, and more recentlytigecycline were considered to be the drugs of choice; however, resistance to these drugs has also been reported. Despite this, they are still being used in areas where resistance has not yet been reported. Use of β-lactamase inhibitors such as sulbactam has been advised in combination with antibiotics to enhance antimicrobial action even in the presence of a 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-resistantP. aeruginosa. Some next-generation antibiotics that are reported as being active againstP. aeruginosa include doripenem, ceftobiprole, and ceftaroline. However, these require more clinical trials for standardization. Therefore, research for the discovery of new antibiotics and drugs againstP. aeruginosa is very much needed.Antibiotics that may have activity againstP. aeruginosa include:
As fluoroquinolones are one of the few antibiotic classes widely effective againstP. aeruginosa, in some hospitals, their use is severely restricted to avoid the development of resistant strains. On the rare occasions where infection is superficial and limited (for example, ear infections or nail infections),topicalgentamicin orcolistin may be used.[citation needed]
For pseudomonal wound infections, acetic acid with concentrations from 0.5% to 5% can be an effective bacteriostatic agent in eliminating the bacteria from the wound. Usually a sterile gauze soaked with acetic acid is placed on the wound after irrigation with normal saline. Dressing would be done once per day. Pseudomonas is usually eliminated in 90% of the cases after 10 to 14 days of treatment.[90]
One of the most worrisome characteristics ofP. aeruginosa is its low antibiotic susceptibility, which is attributable to a concerted action of multidrugefflux pumps with chromosomally encoded antibiotic resistance genes, i.e., the genes that encode proteins that serve asenzymes to break down antibiotics. Examples of such genes are:
Specific genes and enzymes involved in antibiotic resistance can vary between different strains.[104][105]P. aeruginosa TG523 harbored genes predicted to have antibacterial activity and those which are implicated in virulence.[106]
Another feature that contributes to antibiotic resistance ofP. aeruginosa is the low permeability of the bacterial cellular envelopes.[107] In addition to this intrinsic resistance,P. aeruginosa easily develops acquired resistance either bymutation in chromosomally encoded genes or by thehorizontal gene transfer of antibiotic resistance determinants. Development ofmultidrug resistance byP. 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 inP. aeruginosa strains producing chronic infections, whereas the clustering of several different antibiotic resistance genes inintegrons favors the concerted acquisition of antibiotic resistance determinants. Some recent studies have shown phenotypic resistance associated tobiofilm formation or to the emergence of small-colony variants may be important in the response ofP. aeruginosa populations to antibiotic treatment.[70]
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 β-lactamases like PER-1, PER-2, and VEB-1, AmpC cephalosporinases, carbapenemases like serine oxacillinases, metallo-b-lactamases, OXA-type carbapenemases, and aminoglycoside-modifying enzymes, among others, have been reported.P. aeruginosa can also modify the targets of antibiotic action: for example, methylation of 16S rRNA to prevent aminoglycoside binding and modification of DNA, or topoisomerase to protect it from the action of quinolones.P. aeruginosa has also been reported to possess multidrug efflux pumps systems that confer resistance against a number of antibiotic classes, and the MexAB-OprM (Resistance-nodulation-division (RND) family) is considered as the most important[108]. 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.[109]
Mutations inDNA gyrase are commonly associated with antibiotic resistance inP. aeruginosa. These mutations, when combined with others, confer high resistance without hindering survival. Additionally, genes involved in cyclic-di-GMP signaling may contribute to resistance. WhenP. aeruginosa is grown underin vitro conditions designed to mimic a cystic fibrosis patient's lungs, these genes mutate repeatedly.[110]
Twosmall RNAs,Sr0161 andErsA, were shown to interact with mRNA encoding the major porin OprD responsible for the uptake ofcarbapenem antibiotics into theperiplasm. The sRNAs bind to the 5'UTR ofoprD, causing increase in bacterial resistance tomeropenem. Another sRNA,Sr006, may positively regulate (post-transcriptionally) the expression of PagL, an enzyme responsible for deacylation of lipid A. This reduces the pro-inflammatory property of lipid A.[111] Furthermore, similar to a process found inSalmonella,[112] Sr006 regulation of PagL expression may aid inpolymyxin B resistance.[111]
Probiotic prophylaxis may prevent colonization and delay onset ofPseudomonas infection in an ICU setting.[113][non-primary source needed] Immunoprophylaxis againstPseudomonas is being investigated.[114]The risk of contractingP. aeruginosa can be reduced by avoiding pools, hot tubs, and other bodies of standing water; regularly disinfecting and/or replacing equipment that regularly encounters moisture (such as contact lens equipment and solutions); and washing one's hands often (which is protective against many other pathogens as well). However, even the best hygiene practices cannot totally protect an individual againstP. aeruginosa, given how common the organism is in the environment.[115]
Phage therapy againstP. 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.[116]Phage therapy against ear infections caused byP. aeruginosa was reported in the journalClinical Otolaryngology in August 2009.[117] As of 2024,[update] research on the topic is ongoing.[118]
In 2013, João Xavier described an experiment in whichP. aeruginosa, when subjected to repeated rounds of conditions in which it needed to swarm to acquire food, developed the ability to "hyperswarm" at speeds 25% faster than baseline organisms, by developing multipleflagella, whereas the baseline organism has a single flagellum.[119] This result was notable in the field ofexperimental evolution in that it was highly repeatable.[120]P. aeruginosa has been studied for use inbioremediation and use in processingpolyethylene inmunicipal solid waste.[121]
Research on this bacterium'ssystems biology led to the development of genome-scale metabolic models that enable computer simulation and prediction of bacterial growth rates under varying conditions, including its virulence properties.[122][123]
In 2025, a strain ofP. aeruginosa was identified that had gained the ability to produce an enzyme for the metabolism of the plasticpolycaprolactone, commonly used in wound dressings and other medical equipment, enabling it to survive in sterile environments. The bacteria also demonstrated the ability to incorporate plastic intobiofilm, increasing its resistance to antibiotics.[124]
As of 2019[update] theEast African Community considersP. aeruginosa to be aquarantine concern because of the presence ofPhaseolus vulgaris–pathogenic strains ofP. aeruginosa inKenya for the rest of the area. Apest risk analysis by the EAC was based on this bacterium'sCABI's Crop Protection Compendium listing, following Kaaya & Darji 1989's initial detection in Kenya.[125]
A small number of infections in the United States in 2022 and 2023 were likely caused by poorly manufactured eyedrops.[126]
