The small RNA PhrS stimulates synthesis of the <i>Pseudomonas aeruginosa</i> quinolone signal

Sonnleitner, Elisabeth; González, Nicolas; Sorger-Domenigg, Theresa; Heeb, Stephan; Richter, Andreas S.; Backofen, Rolf; Williams, Paul; Hüttenhofer, Alexander; Haas, Dieter; Bläsi, Udo

doi:10.1111/j.1365-2958.2011.07620.x

Cited by 157 publications

(167 citation statements)

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“…1). Our data set also showed a strong role for Anr in regulation of the small RNA PhrS, which is part of the Pseudomonas quinoline system and has been shown to be controlled by Anr previously (58). PhrS levels were reduced 200-fold in PAO1 and 100-fold in J215.…”

Section: Resultsmentioning

confidence: 73%

Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms

et al. 2015

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In Pseudomonas aeruginosa, the transcription factor Anr controls the cellular response to low oxygen or anoxia. Anr activity is high in oxygen-limited environments, including biofilms and populations associated with chronic infections, and Anr is necessary for persistence in a model of pulmonary infection. In this study, we characterized the Anr regulon in biofilm-grown cells at 1% oxygen in the laboratory strain PAO1 and in a quorum sensing (QS)-deficient clinical isolate, J215. As expected, transcripts related to denitrification, arginine fermentation, high-affinity cytochrome oxidases, and CupA fimbriae were lower in the ⌬anr derivatives. In addition, we observed that transcripts associated with quorum sensing regulation, iron acquisition and storage, type VI secretion, and the catabolism of aromatic compounds were also differentially expressed in the ⌬anr strains. Prior reports have shown that quorum sensing-defective mutants have higher levels of denitrification, and we found that multiple Anr-regulated processes, including denitrification, were strongly inversely proportional to quorum sensing in both transcriptional and protein-based assays. We also found that in LasR-defective strains but not their LasR-intact counterparts, Anr regulated the production of the 4-hydroxy-2-alkylquinolines, which play roles in quorum sensing and interspecies interactions. These data show that Anr was required for the expression of important metabolic pathways in low-oxygen biofilms, and they reveal an expanded and compensatory role for Anr in the regulation of virulence-related genes in quorum sensing mutants, such as those commonly isolated from infections. IMPORTANCEPseudomonas aeruginosa causes acute ocular, soft tissue, and pulmonary infections, as well as chronic infections in the airways of cystic fibrosis patients. P. aeruginosa uses quorum sensing (QS) to regulate virulence, but mutations in the gene encoding the master regulator of QS, lasR, are frequently observed in clinical isolates. We demonstrated that the regulon attributed to Anr, an oxygen-sensitive transcription factor, was more highly expressed in lasR mutants. Furthermore, we show that Anr regulates the production of several different secreted factors in lasR mutants. These data demonstrate the importance of Anr in naturally occurring quorum sensing mutants in the context of chronic infections. Pseudomonas aeruginosa, a notorious pulmonary pathogen, is frequently a causative agent of nosocomial pneumonias (1), is commonly isolated from the lungs of chronic obstructive pulmonary disease (COPD) patients experiencing exacerbation (2), and is a problematic colonizer of the lungs of individuals with cystic fibrosis (CF) (3). By age 20, 80% of CF patients harbor P. aeruginosa in their lungs (4), and the presence of P. aeruginosa in the airway is correlated with accelerated lung function decline and poor patient prognosis (5, 6). Evidence suggests that in the context of infections, P. aeruginosa is often found in a biofilm state, which contributes to it...

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Section: Resultsmentioning

confidence: 73%

Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms

et al. 2015

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“…The early induction of Anr may benefit P. aeruginosa in vivo through the induction of high-affinity terminal oxidases that can increase respiration at low oxygen tensions and may also give P. aeruginosa an advantage, as oxygen becomes limiting during biofilm formation or depletion of local oxygen by the host immune response (55). It is also interesting that a small RNA controlled by Anr impacts the expression of quorum sensing-controlled virulence factors such as phenazines (65). Anr also contributes directly to the regulation of genes involved in cyanide biosynthesis (66).…”

Section: Discussionmentioning

confidence: 99%

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

et al. 2013

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bPseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ⌬plcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine betaine (GB), were sufficient to stimulate Anr activity, and their catabolism was required for Anr activation. The addition of choline or GB to glucose-containing medium did not alter Anr protein levels, growth rates, or respiratory activity, and Anr activation could not be attributed to the osmoprotectant functions of GB. The ⌬anr mutant was defective in virulence in a mouse pneumonia model. Several lines of evidence indicate that Anr is important for the colonization of biotic and abiotic surfaces in both P. aeruginosa PAO1 and PA14 and that increases in Anr activity resulted in enhanced biofilm formation. Our data suggest that PlcH activity promotes Anr activity in oxic environments and that Anr activity contributes to virulence, even in the acute infection phase, where low oxygen tensions are not expected. This finding highlights the relationships among in vivo bacterial metabolism, the activity of the oxygen-sensitive regulator Anr, and virulence.

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“…To balance the benefits and costs, secondary metabolism is controlled by complex regulatory networks that regulate production in response to environmental factors and physiological status of the organism producing secondary metabolites (8,9). These networks involve both global and pathway-specific regulators operating to coordinate secondary metabolite biosynthesis pathways at transcriptional and posttranscriptional levels (10)(11)(12).…”

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confidence: 99%

Secondary Metabolism and Interspecific Competition Affect Accumulation of Spontaneous Mutants in the GacS-GacA Regulatory System in Pseudomonas protegens

Yan

Lopes

Shaffer

et al. 2018

mBio

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Secondary metabolites are synthesized by many microorganisms and provide a fitness benefit in the presence of competitors and predators. Secondary metabolism also can be costly, as it shunts energy and intermediates from primary metabolism. In Pseudomonas spp., secondary metabolism is controlled by the GacSGacA global regulatory system. Intriguingly, spontaneous mutations in gacS or gacA (Gac Ϫ mutants) are commonly observed in laboratory cultures. Here we investigated the role of secondary metabolism in the accumulation of Gac Ϫ mutants in Pseudomonas protegens strain Pf-5. Our results showed that secondary metabolism, specifically biosynthesis of the antimicrobial compound pyoluteorin, contributes significantly to the accumulation of Gac Ϫ mutants. Pyoluteorin biosynthesis, which poses a metabolic burden on the producer cells, but not pyoluteorin itself, leads to the accumulation of the spontaneous mutants. Interspecific competition also influenced the accumulation of the Gac Ϫ mutants: a reduced proportion of Gac Ϫ mutants accumulated when P. protegens Pf-5 was cocultured with Bacillus subtilis than in pure cultures of strain Pf-5. Overall, our study associated a fitness trade-off with secondary metabolism, with metabolic costs versus competitive benefits of production influencing the evolution of P. protegens, assessed by the accumulation of Gac Ϫ mutants.IMPORTANCE Many microorganisms produce antibiotics, which contribute to ecologic fitness in natural environments where microbes constantly compete for resources with other organisms. However, biosynthesis of antibiotics is costly due to the metabolic burdens of the antibiotic-producing microorganism. Our results provide an example of the fitness trade-off associated with antibiotic production. Under noncompetitive conditions, antibiotic biosynthesis led to accumulation of spontaneous mutants lacking a master regulator of antibiotic production. However, relatively few of these spontaneous mutants accumulated when a competitor was present. Results from this work provide information on the evolution of antibiotic biosynthesis and provide a framework for their discovery and regulation.KEYWORDS interspecific competition, Pseudomonas, secondary metabolism, spontaneous mutations, GacS-GacA S econdary metabolites play important roles in physiological adaptation and ecologic fitness of the organisms producing secondary metabolites (1, 2). These metabolites vary widely in structure and biological activity, with some having valuable pharmaceu-

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The small RNA PhrS stimulates synthesis of the Pseudomonas aeruginosa quinolone signal

Cited by 157 publications

References 86 publications

Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms

Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

Secondary Metabolism and Interspecific Competition Affect Accumulation of Spontaneous Mutants in the GacS-GacA Regulatory System in Pseudomonas protegens

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