Impact of glycerol-3-phosphate dehydrogenase on virulence factor production by<i>Pseudomonas aeruginosa</i>

Daniels, Jonathan; Scoffield, Jessica; Woolnough, Jessica L.; Silo-Suh, Laura

doi:10.1139/cjm-2014-0485

Cited by 18 publications

(15 citation statements)

References 45 publications

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“…Although increased expression of the phospholipase genes was not observed under LS conditions, genes involved in glycerol uptake ( glpF ) and metabolism ( glpK , glpD ) were upregulated ≥1.50-fold under LS conditions. Recently, it was shown that CF-adapted P. aeruginosa isolates utilize glycerol as a carbon source more efficiently than nonadapted isolates ( 57 ). In addition, mutation of the glpD gene (encoding a glycerol-3-phosphate dehydrogenase) resulted in lower levels of alginate production, indicating that the glycerol catabolic pathway is indispensable for full virulence of P. aeruginosa in chronic CF infection ( 57 ).…”

Section: Resultsmentioning

confidence: 99%

Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung

Dingemans

Monsieurs

et al. 2016

mBio

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Chronic colonization of the lungs by Pseudomonas aeruginosa is one of the major causes of morbidity and mortality in cystic fibrosis (CF) patients. To gain insights into the characteristic biofilm phenotype of P. aeruginosa in the CF lungs, mimicking the CF lung environment is critical. We previously showed that growth of the non-CF-adapted P. aeruginosa PAO1 strain in a rotating wall vessel, a device that simulates the low fluid shear (LS) conditions present in the CF lung, leads to the formation of in-suspension, self-aggregating biofilms. In the present study, we determined the phenotypic and transcriptomic changes associated with the growth of a highly adapted, transmissible P. aeruginosa CF strain in artificial sputum medium under LS conditions. Robust self-aggregating biofilms were observed only under LS conditions. Growth under LS conditions resulted in the upregulation of genes involved in stress response, alginate biosynthesis, denitrification, glycine betaine biosynthesis, glycerol metabolism, and cell shape maintenance, while genes involved in phenazine biosynthesis, type VI secretion, and multidrug efflux were downregulated. In addition, a number of small RNAs appeared to be involved in the response to shear stress. Finally, quorum sensing was found to be slightly but significantly affected by shear stress, resulting in higher production of autoinducer molecules during growth under high fluid shear (HS) conditions. In summary, our study revealed a way to modulate the behavior of a highly adapted P. aeruginosa CF strain by means of introducing shear stress, driving it from a biofilm lifestyle to a more planktonic lifestyle.

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Section: Resultsmentioning

confidence: 99%

Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung

Dingemans

Monsieurs

et al. 2016

mBio

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“…For example, genes that encode the 'acetate switch', permitting a transition from rapid growth to a slower, acetatescavenging lifestyle [52], as well as dehydrogenases, hydratases and anaerobic reductases were identi ed only in LAP. Anaerobic glycerol phosphate-3-hydrogenase genes, which play a critical role in utilizing alternate nutritional sources [53] were consistently higher in LAP when compared to the other two. Genes encoding c-type cytochrome and molybdenum cofactor biosynthesis, iron-sulfur clusters, and formate dehydrogenase were also overrepresented in this cohort.…”

Section: Discussionmentioning

confidence: 94%

Metagenomic Sequencing of Stage 3 Periodontitis Reveals Phenotype-Specific Taxonomic and Functional Features of the Subgingival Microbiome

Altabtbaei

Maney

Ganesan

et al. 2020

Preprint

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Background: The search for microbial biomarkers of periodontitis has been hampered by our ability to separate disease-specific associations from those that are common to all forms of periodontitis. Here, we present the first functional characterization of the microbiomes of three common clinical phenotypes of this disease: Localized aggressive periodontitis (LAP), generalized aggressive periodontitis (GAP) and chronic periodontitis (CP). Methods: We collected subgingival plaque samples from sites with disease of 59 subjects with Stage 3 periodontitis and 25 periodontally healthy individuals and used shotgun metagenomics to characterize the aggregate of bacterial genes. Results: Beta-dispersion metrics demonstrated that no two individuals with disease, especially those with chronic disease, are alike (the Anna Karenina Principle), indicating that microbial modulation therapies will have to incorporate patient-specific parameters for efficacy. We discovered broad patterns of microbial dysbiosis that spanned the three disease phenotypes, as well as disease-specific indicators unique to each phenotype. Genes common to all forms of periodontitis encoded pathways that facilitate life in an oxygen-poor, protein and heme-rich, pro-oxidant environment, and enhance capacity for attachment and biofilm formation, while genes encoding the acetate switch, c-type cytochrome and molybdenum cofactor biosynthesis, iron-sulfur clusters, and formate dehydrogenase were unique to LAP. These can serve as potential biomarkers for molecular identification of clinical phenotypes and clarify the role of the microbiome in disease pathogenesis. We also discovered that clinical phenotypes of disease resolved variance in the microbiome with greater clarity than the newly established grading system. Importantly, we observed that one-third of the metagenome of LAP is unique to this phenotype while GAP shares significant functional and taxonomic features with both LAP and CP, suggesting either attenuation of an aggressive disease or an early-onset chronic disease. Conclusion: Within the limitations of a small sample size and a cross-sectional study design, the distinctive features of the microbiomes associated with LAP and CP strongly persuade us that these are discrete disease entities, while calling into question whether GAP is a separate disease entity, or an artifact induced by cross-sectional study designs.

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“…We previously reported that the P. aeruginosa CF isolate, FRD1, displays a growth advantage when grown on glycerol compared to the wound isolate, PAO1 (Daniels et al 2014). Moreover, we demonstrated that glycerol-3-phosphate dehydrogenase, (glpD), is required for the optimal production of key P. aeruginosa virulence factors, including alginate production by FRD1, suggesting that glycerol metabolism may be an important factor that mediates persistence by some chronic isolates of P. aeruginosa.…”

Section: Growth On Glycerol and Deregulation Of Glycerol Metabolism Pmentioning

confidence: 88%

“…Our laboratory previously reported that the chronic CF isolate, FRD1, has a growth advantage on glycerol compared to the acute isolate, PAO1. In addition, we demonstrated that glycerol-3-phosphate (glpD) is required for the production of some P. aeruginosa virulence factors, including alginate (Daniels et al 2014), which has been shown to play an important role in biofilm architecture and protection from antimicrobials (Hentzer et al 2001). Not surprisingly, 80% of chronic infections are associated with microbial biofilm formation (Costerton et al 1999).…”

Section: R a F Tmentioning

confidence: 99%

Glycerol metabolism promotes biofilm formation byPseudomonas aeruginosa

Scoffield

Silo-Suh

2016

Can. J. Microbiol.

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Pseudomonas aeruginosa causes persistent infections in the airways of cystic fibrosis (CF) patients. Airway sputum contains various host-derived nutrients that can be utilized by P. aeruginosa, including phosphotidylcholine, a major component of host cell membranes. Phosphotidylcholine can be degraded by P. aeruginosa to glycerol and fatty acids to increase the availability of glycerol in the CF lung. In this study, we explored the role that glycerol metabolism plays in biofilm formation by P. aeruginosa. We report that glycerol metabolism promotes biofilm formation by both a chronic CF isolate (FRD1) and a wound isolate (PAO1) of P. aeruginosa. Moreover, loss of the GlpR regulator, which represses the expression of genes involved in glycerol metabolism, enhances biofilm formation in FRD1 through the upregulation of Pel polysaccharide. Taken together, our results suggest that glycerol metabolism may be a key factor that contributes to P. aeruginosa persistence by promoting biofilm formation.

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Impact of glycerol-3-phosphate dehydrogenase on virulence factor production byPseudomonas aeruginosa

Cited by 18 publications

References 45 publications

Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung

Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung

Metagenomic Sequencing of Stage 3 Periodontitis Reveals Phenotype-Specific Taxonomic and Functional Features of the Subgingival Microbiome

Glycerol metabolism promotes biofilm formation byPseudomonas aeruginosa

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