The limits to growth – energetic burden of the endogenous antibiotic tropodithietic acid in Phaeobacter inhibens DSM 17395

ABSTRACTTropodithietic acid (TDA) is an antibacterial compound produced by somePhaeobacterandRuegeriaspp. of theRoseobacterclade. TDA production is studied in marine broth or agar since antibacterial activity in other media is not observed. The purpose of this study was to determine how TDA production is influenced by substrate components. High concentrations of ferric citrate, as present in marine broth, or other iron sources were required for production of antibacterially active TDA. However, when supernatants of noninhibitory, low-iron cultures ofPhaeobacter inhibenswere acidified, antibacterial activity was detected in a bioassay. The absence of TDA in nonacidified cultures and the presence of TDA in acidified cultures were verified by liquid chromatography–high-resolution mass spectrometry. A noninhibitory TDA analog (pre-TDA) was produced byP. inhibens,Ruegeria mobilisF1926, andPhaeobactersp. strain 27-4 under low-iron concentrations and was instantaneously converted to TDA when pH was lowered. Production of TDA in the presence of Fe3+coincides with formation of a dark brown substance, which could be precipitated by acid addition. From this brown pigment TDA could be liberated slowly with aqueous ammonia, and both direct-infusion mass spectrometry and elemental analysis indicated a [FeIII(TDA)2]xcomplex. The pigment could also be produced by precipitation of pure TDA with FeCl3. Our results raise questions about how biologically active TDA is produced in natural marine settings where iron is typically limited and whether the affinity of TDA to iron points to a physiological or ecological function of TDA other than as an antibacterial compound.

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Biofilm formation is not a prerequisite for production of the antibacterial compound tropodithietic acid in Phaeobacter inhibens DSM17395

Journal of Applied Microbiology ◽

10.1111/jam.12659 ◽

2014 ◽

Vol 117 (6) ◽

pp. 1592-1600 ◽

Cited By ~ 12

Author(s):

M.J. Prol García ◽

P.W. D'Alvise ◽

A.M. Rygaard ◽

L. Gram

Keyword(s):

Biofilm Formation ◽

Tropodithietic Acid ◽

Antibacterial Compound ◽

Phaeobacter Inhibens

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Genomic evolution of the marine bacterium Phaeobacter inhibens during biofilm growth

Applied and Environmental Microbiology ◽

10.1128/aem.00769-21 ◽

2021 ◽

Author(s):

Marwan E. Majzoub ◽

Kerensa McElroy ◽

Michael Maczka ◽

Stefan Schulz ◽

Torsten Thomas ◽

...

Keyword(s):

Genome Evolution ◽

Phenotypic Variation ◽

Phenotypic Diversity ◽

Survival Strategies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Biofilm Growth ◽

Tropodithietic Acid ◽

Biofilm Dispersal ◽

Phaeobacter Inhibens

P. inhibens 2.10 is an effective biofilm former on marine surfaces and has the ability to outcompete other microorganisms, possibly due to the production of the plasmid-encoded, secondary metabolite tropodithietic acid (TDA). P. inhibens 2.10 biofilms produce phenotypic variants with reduced competitiveness compared to the wild-type. In the present study, we used longitudinal, genome-wide deep sequencing to uncover the genetic foundation that contributes to the emergent phenotypic diversity in P. inhibens 2.10 biofilm dispersants. Our results show that phenotypic variation is not due to the loss of plasmid that encodes the genes for the TDA synthesis, but instead show that P. inhibens 2.10 biofilm populations become rapidly enriched in single nucleotide variations in genes involved in the synthesis of TDA. While variants in genes previously linked to other phenotypes, such as lipopolysaccharide production (i.e. rfbA ) and celluar persistence (i.e. metG ), also appear to be selected for during biofilm dispersal, the number and consistency of variations found for genes involved in TDA production suggest that this metabolite imposes a burden for P. inhibens 2.10 cells. Our results indicate a strong selection pressure for the loss of TDA in mono-species biofilm populations and provide insight into how competition (or lack thereof) in biofilms might shape genome evolution in bacteria. Importance Statement Biofilm formation and dispersal are important survival strategies for environmental bacteria. During biofilm dispersal cells often display stable and heritable variants from the parental biofilm. Phaeobacter inhibens is an effective colonizer of marine surfaces, in which a subpopulation of its biofilm dispersal cells displays a non-competitive phenotype. This study aimed to elucidate the genetic basis of these phenotypic changes. Despite the progress made to date in characterizing the dispersal variants in P. inhibens , little is understood about the underlying genetic changes that result in the development of the specific variants. Here, P. inhibens phenotypic variation was linked to single nucleotide polymorphisms (SNPs), in particular in genes affecting the competitive ability of P. inhibens , including genes related to the production of the antibiotic tropodithietic acid (TDA) and bacterial cell-cell communication (e.g. quorum sensing). This work is significant as it reveals how the biofilm-lifestyle might shape genome evolution in a cosmopolitan bacterium.

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Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.10.188 ◽

2014 ◽

Vol 10 ◽

pp. 1796-1801 ◽

Cited By ~ 6

Author(s):

Patrick Rabe ◽

Tim A Klapschinski ◽

Nelson L Brock ◽

Christian A Citron ◽

Paul D’Alvise ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Vibrio Anguillarum ◽

Antibiotic Activity ◽

Synthetic Compounds ◽

Tropodithietic Acid ◽

Structure Activity ◽

Structural Analogues ◽

Sar Study ◽

Sulfur Containing ◽

Phaeobacter Inhibens

Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from theRoseobacterclade bacteriumPhaeobacter inhibensDSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests againstStaphylococcus aureusandVibrio anguillarumfor a structure–activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed.

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Biosynthesis of the antibiotic tropodithietic acid by the marine bacterium Phaeobacter inhibens

Chemical Communications ◽

10.1039/c4cc01924e ◽

2014 ◽

Vol 50 (41) ◽

pp. 5487 ◽

Cited By ~ 45

Author(s):

Nelson L. Brock ◽

Alexander Nikolay ◽

Jeroen S. Dickschat

Keyword(s):

Marine Bacterium ◽

Tropodithietic Acid ◽

Phaeobacter Inhibens

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Toxicity of Bioactive and Probiotic Marine Bacteria and Their Secondary Metabolites in Artemia sp. and Caenorhabditis elegans as Eukaryotic Model Organisms

Applied and Environmental Microbiology ◽

10.1128/aem.02717-13 ◽

2013 ◽

Vol 80 (1) ◽

pp. 146-153 ◽

Cited By ~ 28

Author(s):

Anna Katrin Neu ◽

Maria Månsson ◽

Lone Gram ◽

María J. Prol-García

Keyword(s):

Adverse Effect ◽

Caenorhabditis Elegans ◽

Side Effects ◽

Point Of View ◽

Model Organisms ◽

Content Type ◽

Tropodithietic Acid ◽

Antibiotic Compounds ◽

Eukaryotic Organisms ◽

Phaeobacter Inhibens

ABSTRACTWe have previously reported that some strains belonging to the marineActinobacteriaclass, thePseudoalteromonasgenus, theRoseobacterclade, and thePhotobacteriaceaeandVibrionaceaefamilies produce both antibacterial and antivirulence compounds, and these organisms are interesting from an applied point of view as fish probiotics or as a source of pharmaceutical compounds. The application of either organisms or compounds requires that they do not cause any side effects, such as toxicity in eukaryotic organisms. The purpose of this study was to determine whether these bacteria or their compounds have any toxic side effects in the eukaryotic organismsArtemiasp. andCaenorhabditis elegans.Arthrobacter davidanieliWX-11,Pseudoalteromonas luteoviolaceaS4060,P. piscicidaS2049,P. rubraS2471,Photobacterium halotoleransS2753, andVibrio coralliilyticusS2052 were lethal to either or both model eukaryotes. The toxicity ofP. luteoviolaceaS4060 could be related to the production of the antibacterial compound pentabromopseudilin, while the adverse effect observed in the presence ofP. halotoleransS2753 andV. coralliilyticusS2052 could not be explained by the production of holomycin nor andrimid, the respective antibiotic compounds in these organisms. In contrast, the tropodithietic acid (TDA)-producing bacteriaPhaeobacter inhibensDSM17395 andRuegeria mobilisF1926 and TDA itself had no adverse effect on the target organisms. These results reaffirm TDA-producingRoseobacterbacteria as a promising group to be used as probiotics in aquaculture, whereasActinobacteria,Pseudoalteromonas,Photobacteriaceae, andVibrionaceaeshould be used with caution.

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The limits to growth and the limits of psychology.

American Psychologist ◽

10.1037/0003-066x.33.7.701 ◽

1978 ◽

Vol 33 (7) ◽

pp. 701-703 ◽

Cited By ~ 2

Author(s):

Paul C. Stern

Keyword(s):

Limits To Growth

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Oil Prices: Limits to Growth and the Depth of Falling

Voprosy Ekonomiki ◽

10.32609/0042-8736-2006-3-28-41 ◽

2006 ◽

pp. 28-41 ◽

Cited By ~ 6

Author(s):

I. Bashmakov

Keyword(s):

Energy Demand ◽

Negative Relationship ◽

Oil Prices ◽

Production Factor ◽

Energy Costs ◽

Purchasing Power ◽

Limits To Growth ◽

Technological Basis ◽

Production Factors ◽

Output Ratio

This article deals with the determination of future oil prices. The approach used is based on the evaluation of purchasing power limits and allows to put the limits to monopolistic price setting. Several important findings are formulated: going beyond the upper thresholds of purchasing power stipulates negative relationship between energy costs and GDP growth rates, and this brings the dynamics to energy demand to price elasticity. This approach is also based on what the author calls the economics of constants and variables, i.e. on the existence of very stable macroeconomic proportions, which may be observed throughout the whole period of statistical observations (over 200 years). It provides grounds for two conclusions. First, the upper limit of energy costs to the gross output ratio is determined by the least acceptable profitability. Second, the theoretical postulate on substantial production factors substitution used in the production functions theory may be incorrect. In reality, the change of the economy technological basis leads to the substitution of low quality production factor by the same factor with a higher quality. Application of this approach brings the basis for predicting oil prices for 2006-2008.

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