Pseudomonas aeruginosa is a bacterium commonly found across various environments, including soil, water, and even within living organisms. Its metabolic capabilities allow it to thrive in diverse conditions and contribute to its ability to cause infections.
Core Metabolic Pathways
P. aeruginosa primarily generates energy through aerobic respiration, a highly efficient process. This method involves oxidative phosphorylation, where electrons are transferred through a branched electron transport chain to oxygen as the final acceptor. The bacterium possesses a complex respiratory chain with various dehydrogenases and multiple terminal oxidases that reduce oxygen to water, fueling cellular activities.
When oxygen becomes scarce, P. aeruginosa demonstrates its metabolic flexibility by switching to anaerobic respiration, specifically through denitrification. In this process, the bacterium utilizes nitrogen oxides, such as nitrate, as alternative electron acceptors. Nitrate is sequentially reduced to nitrite, nitric oxide, nitrous oxide, and ultimately to dinitrogen gas. This pathway is regulated by systems like Anr and Dnr, enabling the bacterium to sustain growth in oxygen-depleted environments, such as those found in some infections.
For processing basic carbon sources like glucose, P. aeruginosa mainly employs the Entner-Doudoroff (ED) pathway. Unlike many other bacteria that use the Embden-Meyerhof-Parnas (EMP) pathway for glycolysis, P. aeruginosa lacks phosphofructokinase, an enzyme necessary for EMP pathway function. The ED pathway converts glucose to glyceraldehyde-3-phosphate and pyruvate, which then feed into the tricarboxylic acid (TCA) cycle for further energy generation. The bacterium also performs gluconeogenesis, synthesizing glucose from non-carbohydrate precursors.
Metabolic Adaptability and Nutrient Utilization
P. aeruginosa exhibits remarkable metabolic adaptability, allowing it to utilize a wide array of organic compounds beyond simple sugars. It can metabolize various carbon sources, including fatty acids, amino acids, and aromatic compounds. For instance, fatty acids, abundant in environments like the cystic fibrosis airway, are degraded through specific fatty acyl-CoA dehydrogenases, such as FadE1 and FadE2, which show preferences for long- and medium-chain fatty acids, respectively.
The bacterium also demonstrates versatility in nitrogen metabolism, utilizing various inorganic and organic nitrogen sources. It can assimilate ammonia, nitrate, and various amino acids to fulfill its nitrogen requirements. The assimilatory nitrate reduction system, regulated by the NasS/T two-component system, allows it to use nitrate and nitrite as nitrogen sources. Beyond assimilation, its denitrification pathway converts nitrogen oxides into atmospheric nitrogen gas.
Iron acquisition is a particularly important aspect of P. aeruginosa’s metabolism, especially within a host where iron is often scarce. The bacterium produces small, high-affinity iron-chelating molecules called siderophores, primarily pyoverdine and pyochelin.
Pyoverdine is considered the primary siderophore due to its high iron-chelating affinity and its dual role in not only scavenging iron but also acting as a signaling molecule for virulence factor production. Pyochelin, while having a lower affinity, also contributes to iron uptake. These siderophores bind ferric iron (Fe3+) in the environment and transport it into the bacterial cell via specific receptors.
P. aeruginosa’s metabolic flexibility allows it to quickly adjust its metabolic pathways in response to changing nutrient availability and stress conditions. This capacity helps it persist in challenging environments, including the nutrient-heterogeneous conditions found in infected tissues.
Metabolism and Virulence
The metabolic capabilities of P. aeruginosa are closely linked to its ability to cause disease, particularly through biofilm formation. Biofilms are communities of bacteria embedded in a self-produced matrix of extracellular polymeric substances (EPS), which provides protection and facilitates persistence. Metabolic processes supply the energy and building blocks required for synthesizing these EPS components, such as Pel and Psl polysaccharides. Within biofilms, nutrient gradients can form, influencing the metabolic activity and gene expression of cells located at different depths.
Metabolism also fuels the production of various virulence factors that contribute to P. aeruginosa’s pathogenicity. Energy and precursor molecules derived from central metabolic pathways are channeled into synthesizing exotoxins, such as exotoxin A, which can damage host cells by inhibiting protein synthesis. Proteases like elastase are produced, breaking down host tissues and immune components. Furthermore, the bacterium synthesizes pigments like pyocyanin, a blue-green phenazine that generates reactive oxygen species, causing cellular damage and interfering with host immune responses.
Quorum sensing (QS) systems, which allow bacteria to communicate and coordinate collective behaviors based on population density, are intertwined with metabolism. P. aeruginosa employs multiple QS circuits, including the Las, Rhl, and PQS systems, which utilize acyl-homoserine lactone and quinolone signals. These systems regulate the expression of hundreds of genes, many of which are involved in virulence factor production and biofilm formation. Metabolic signals can influence QS, and conversely, QS can induce widespread metabolic rearrangements within the cell, altering the production of metabolites and impacting cellular metabolic fluxes.
Metabolic adaptations also contribute to P. aeruginosa’s notable antibiotic resistance. Overexpression of multidrug efflux pumps, such as MexAB-OprM, MexXY, MexCD-OprJ, and MexEF-OprN, allows the bacterium to actively pump antibiotics out of the cell. These efflux pumps are large protein complexes that require metabolic energy for their synthesis and function. To compensate for the energy costs associated with overexpressing these transporters, P. aeruginosa can undergo metabolic rewiring, sometimes increasing anaerobic nitrate respiration to balance intracellular pH and energy demands.