Discovery of an operon that participates in agmatine metabolism and regulates biofilm formation in <i>Pseudomonas aeruginosa</i>

Williams, Bryan J.; Du, Rui; Calcutt, M. Wade; Abdolrasulnia, Rasul; Christman, Brian W.; Blackwell, Timothy S.

doi:10.1111/j.1365-2958.2010.07083.x

Cited by 29 publications

(43 citation statements)

References 53 publications

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“…To date, only five of these candidates have been experimentally shown to be Tat substrates: two secreted phospholipases16 and three periplasmic proteins involved in pyoverdine biosynthesis and agmatine metabolism383940. However, in silico approaches can only provide an estimate of the true number of Tat substrates and cannot predict whether a protein exported into the periplasm will subsequently be secreted through the OM.…”

Section: Discussionmentioning

confidence: 99%

Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa

Ball¹,

Antelmann²,

Imbert³

et al. 2016

Sci Rep

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The opportunistic pathogen Pseudomonas aeruginosa uses secretion systems to deliver exoproteins into the environment. These exoproteins contribute to bacterial survival, adaptation, and virulence. The Twin arginine translocation (Tat) export system enables the export of folded proteins into the periplasm, some of which can then be further secreted outside the cell. However, the full range of proteins that are conveyed by Tat is unknown, despite the importance of Tat for the adaptability and full virulence of P. aeruginosa. In this work, we explored the P. aeruginosa Tat-dependent exoproteome under phosphate starvation by two-dimensional gel analysis. We identified the major secreted proteins and new Tat-dependent exoproteins. These exoproteins were further analyzed by a combination of in silico analysis, regulation studies, and protein localization. Altogether we reveal that the absence of the Tat system significantly affects the composition of the exoproteome by impairing protein export and affecting gene expression. Notably we discovered three new Tat exoproteins and one novel type II secretion substrate. Our data also allowed the identification of two new start codons highlighting the importance of protein annotation for subcellular predictions. The new exoproteins that we identify may play a significant role in P. aeruginosa pathogenesis, host interaction and niche adaptation.

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Section: Discussionmentioning

confidence: 99%

Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa

Ball¹,

Antelmann²,

Imbert³

et al. 2016

Sci Rep

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“…Prior to the analysis, samples were supplemented with internal standard, homoagmatine (hAgm)[19], and purified by centrifugation with Amicon centrifugal filters (Millipore) at 14000 × g, for 10 min., at room temp. The resulting filtrate was then evaporated under N 2 gas and reconstituted with 50% acetonitrile containing 100 mM NaHCO 3 (pH 8.0) and derivatized with 20 mM dansyl chloride (Sigma) at 50°C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Reduced bioavailable manganese causes striatal urea cycle pathology in Huntington's disease mouse model

Bichell

Węgrzynowicz

Tipps

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Huntington’s disease (HD) is caused by a mutation in the huntingtin gene (HTT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model. Further, either in vivo or in vitro Mn supplementation reverses the urea-cycle pathology by restoring arginase activity. We show that Arginase 2 (ARG2) is the arginase enzyme present in these mouse brain models, with ARG2 protein levels directly increased by Mn exposure. ARG2 protein is not reduced in the prodromal stage, though enzyme activity is reduced, indicating that altered Mn bioavailability as a cofactor leads to the deficient enzymatic activity. These data support a hypothesis that mutant HTT leads to a selective deficiency of neuronal Mn at an early disease stage, contributing to HD striatal urea-cycle pathophysiology through an effect on arginase activity.

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“…We also include the production of rhamnolipids due to their role in biofilm formation and regulation, as previously mentioned. Intracellular signaling molecules such as the polyamines putrescine and spermidine are not essential for growth in many environments, but their loss induces significant phenotypic changes in various bacteria and they are considered important in the regulation of biofilm production and other virulence pathways (65). Ornibactin enables iron acquisition, and salicylate potentially acts as a siderophore and is also required for production of other siderophores; both compounds have been connected with enhanced virulence both clinically and in animal models (48).…”

Section: Metabolic Network Reconstructionsmentioning

confidence: 99%

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

Bartell¹,

Yen²,

Varga³

et al. 2013

Journal of Bacteriology

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Burkholderia cenocepacia and Burkholderia multivorans are opportunistic drug-resistant pathogens that account for the majority of Burkholderia cepacia complex infections in cystic fibrosis patients and also infect other immunocompromised individuals. While they share similar genetic compositions, B. cenocepacia and B. multivorans exhibit important differences in pathogenesis. We have developed reconciled genome-scale metabolic network reconstructions of B. cenocepacia J2315 and B. multivorans ATCC 17616 in parallel (designated iPY1537 and iJB1411, respectively) to compare metabolic abilities and contextualize genetic differences between species. The reconstructions capture the metabolic functions of the two species and give insight into similarities and differences in their virulence and growth capabilities. The two reconstructions have 1,437 reactions in common, and iPY1537 and iJB1411 have 67 and 36 metabolic reactions unique to each, respectively. After curating the extensive reservoir of metabolic genes in Burkholderia, we identified 6 genes essential to growth that are unique to iPY1513 and 13 genes uniquely essential to iJB1411. The reconstructions were refined and validated by comparing in silico growth predictions to in vitro growth capabilities of B. cenocepacia J2315, B. cenocepacia K56-2, and B. multivorans ATCC 17616 on 104 carbon sources. Overall, we identified functional pathways that indicate B. cenocepacia can produce a wider array of virulence factors compared to B. multivorans, which supports the clinical observation that B. cenocepacia is more virulent than B. multivorans. The reconciled reconstructions provide a framework for generating and testing hypotheses on the metabolic and virulence capabilities of these two related emerging pathogens. Multidrug-resistant pathogens are a severe health concern and can cause chronic infections in a variety of patient populations with limited recourse for treatment. Here, we investigate two multidrug-resistant species, Burkholderia cenocepacia and Burkholderia multivorans, of the Burkholderia cepacia complex (BCC) which are considered dangerous and difficult to treat in patients with cystic fibrosis (CF), chronic granulomatous disease, or compromised immune systems (1). With larger genomes (8.06 Mbp and 7.01 Mbp, respectively) than many other multidrug-resistant pathogens, they also contain an expanded reservoir of genes that may assist their ability to avoid clinical eradication (2-4). Because they are nosocomial, transmissible between patients, and also routinely acquired (and reacquired) from the environment, B. cenocepacia and B. multivorans are the two BCC species most commonly isolated from the sputum of CF patients (5-8). In patients with CF, pulmonary infection with BCC can contribute to the rapid deterioration of lung function known as cepacia syndrome, a necrotizing pneumonia that can lead to bacteremia, septicemia, and increased mortality (9, 10). A combination of high antibiotic resistance and decreased immune function in patients makes B. cen...

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Discovery of an operon that participates in agmatine metabolism and regulates biofilm formation in Pseudomonas aeruginosa

Cited by 29 publications

References 53 publications

Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa

Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa

Reduced bioavailable manganese causes striatal urea cycle pathology in Huntington's disease mouse model

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

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