BdcA, a Protein Important for Escherichia coli Biofilm Dispersal, Is a Short-Chain Dehydrogenase/Reductase that Binds Specifically to NADPH

Lord, Dana M.; Baran, Ayşe Uzgören; Wood, Thomas K.; Peti, Wolfgang; Page, Rebecca

doi:10.1371/journal.pone.0105751

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…BlastP analysis of Cj0485 indicates that the protein is homologous to short chain dehydrogenase enzymes that are generally involved in metabolism of compounds such as carbohydrates, amino acids and lipids (Kavanagh et al ., ; Bijtenhoorn et al ., ). Recent findings have also implicated dehydrogenases in quorum sensing pathways in bacteria (Lord et al ., ). It is possible that cj0485 encodes a protein that is involved in both fucose metabolism and sensing.…”

Section: Discussionmentioning

confidence: 97%

L‐fucose influences chemotaxis and biofilm formation in Campylobacter jejuni

Dwivedi

Nothaft

Garber

et al. 2016

Molecular Microbiology

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Campylobacter jejuni and Campylobacter coli are zoonotic pathogens once considered asaccharolytic, but are now known to encode pathways for glucose and fucose uptake/metabolism. For C. jejuni, strains with the fuc locus possess a competitive advantage in animal colonization models. We demonstrate that this locus is present in > 50% of genome-sequenced strains and is prevalent in livestock-associated isolates of both species. To better understand how these campylobacters sense nutrient availability, we examined biofilm formation and chemotaxis to fucose. C. jejuni NCTC11168 forms less biofilms in the presence of fucose, although its fucose permease mutant (fucP) shows no change. In a newly developed chemotaxis assay, both wild-type and the fucP mutant are chemotactic towards fucose. C. jejuni 81-176 naturally lacks the fuc locus and is unable to swim towards fucose. Transfer of the NCTC11168 locus into 81-176 activated fucose uptake and chemotaxis. Fucose chemotaxis also correlated with possession of the pathway for C. jejuni RM1221 (fuc+) and 81116 (fuc-). Systematic mutation of the NCTC11168 locus revealed that Cj0485 is necessary for fucose metabolism and chemotaxis. This study suggests that components for fucose chemotaxis are encoded within the fuc locus, but downstream signals only in fuc + strains, are involved in coordinating fucose availability with biofilm development.

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Section: Discussionmentioning

confidence: 97%

L‐fucose influences chemotaxis and biofilm formation in Campylobacter jejuni

Dwivedi

Nothaft

Garber

et al. 2016

Molecular Microbiology

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“…These ‘sequestration molecules’ may not directly act upon biofilm microbes, but by reducing the levels of important secondary messengers, metabolites, and nutrients, active dispersal can be triggered. For example, BdcA is a protein produced by E. coli that binds free c-di-GMP, indirectly inhibiting biofilm by blocking the molecule’s biofilm-producing and biofilm-sustaining cellular pathways [ 113 , 114 , 115 ].…”

Section: Dispersal Moleculesmentioning

confidence: 99%

Approaches to Dispersing Medical Biofilms

2017

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Biofilm-associated infections pose a complex problem to the medical community, in that residence within the protection of a biofilm affords pathogens greatly increased tolerances to antibiotics and antimicrobials, as well as protection from the host immune response. This results in highly recalcitrant, chronic infections and high rates of morbidity and mortality. Since as much as 80% of human bacterial infections are biofilm-associated, many researchers have begun investigating therapies that specifically target the biofilm architecture, thereby dispersing the microbial cells into their more vulnerable, planktonic mode of life. This review addresses the current state of research into medical biofilm dispersal. We focus on three major classes of dispersal agents: enzymes (including proteases, deoxyribonucleases, and glycoside hydrolases), antibiofilm peptides, and dispersal molecules (including dispersal signals, anti-matrix molecules, and sequestration molecules). Throughout our discussion, we provide detailed lists and summaries of some of the most prominent and extensively researched dispersal agents that have shown promise against the biofilms of clinically relevant pathogens, and we catalog which specific microorganisms they have been shown to be effective against. Lastly, we discuss some of the main hurdles to development of biofilm dispersal agents, and contemplate what needs to be done to overcome them.

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“…For example, the irreversible duplicates for several reactions including acetolactate synthase, aconitase, phosphoribosylaminoimidazole carboxylase, alcohol-NAD oxidoreductase, arginine deiminase, D-ribitol-5-phosphate NAD 2-oxidoreductase, glycerate dehydrogenase, methionine synthase, and ribokinase were removed. Also, based on available cofactor specificity information, 51,52 reactions such as cytidine kinase (GTP), glycerol-3-phosphate dehydrogenase (NAD), guanylate kinase (GMP:dATP), and homoserine dehydrogenase (NADH) were turned off to ensure correct cofactor usage in these reactions. Reactions involved in polyamine synthesis and degradation were removed due to the lack of convincing evidence of polyamine metabolism in S. aureus USA300_FPR3757.…”

Section: Resultsmentioning

confidence: 99%

An integrated computational and experimental study to investigate Staphylococcus aureus metabolism

et al. 2020

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Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is essential to understand its pathogenesis. To this end, we have reconstructed and experimentally validated an updated and enhanced genome-scale metabolic model of S. aureus USA300_FPR3757. The model combined genome annotation data, reaction stoichiometry, and regulation information from biochemical databases and previous strain-specific models. Reactions in the model were checked and fixed to ensure chemical balance and thermodynamic consistency. To further refine the model, growth assessment of 1920 nonessential mutants from the Nebraska Transposon Mutant Library was performed, and metabolite excretion profiles of important mutants in carbon and nitrogen metabolism were determined. The growth and no-growth inconsistencies between the model predictions and in vivo essentiality data were resolved using extensive manual curation based on optimization-based reconciliation algorithms. Upon intensive curation and refinements, the model contains 863 metabolic genes, 1379 metabolites (including 1159 unique metabolites), and 1545 reactions including transport and exchange reactions. To improve the accuracy and predictability of the model to environmental changes, condition-specific regulation information curated from the existing knowledgebase was incorporated. These critical additions improved the model performance significantly in capturing gene essentiality, substrate utilization, and metabolite production capabilities and increased the ability to generate model-based discoveries of therapeutic significance. Use of this highly curated model will enhance the functional utility of omics data, and therefore, serve as a resource to support future investigations of S. aureus and to augment staphylococcal research worldwide.npj Systems Biology and Applications (2020) 6:3 ; https://doi.

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BdcA, a Protein Important for Escherichia coli Biofilm Dispersal, Is a Short-Chain Dehydrogenase/Reductase that Binds Specifically to NADPH

Cited by 20 publications

References 43 publications

L‐fucose influences chemotaxis and biofilm formation in Campylobacter jejuni

L‐fucose influences chemotaxis and biofilm formation in Campylobacter jejuni

Approaches to Dispersing Medical Biofilms

An integrated computational and experimental study to investigate Staphylococcus aureus metabolism

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