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

Abstract

bWe have previously reported that some strains belonging to the marine Actinobacteria class, the Pseudoalteromonas genus, the Roseobacter clade, and the Photobacteriaceae and Vibrionaceae families 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 organisms Artemia sp. and Caenorhabditis elegans. Arthrobacter davidanieli WX-11, Pseudoalteromonas luteoviolacea S4060, P. piscicida S2049, P. rubra S2471, Photobacterium halotolerans S2753, and Vibrio coralliilyticus S2052 were lethal to either or both model eukaryotes. The toxicity of P. luteoviolacea S4060 could be related to the production of the antibacterial compound pentabromopseudilin, while the adverse effect observed in the presence of P. halotolerans S2753 and V. coralliilyticus S2052 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 bacteria Phaeobacter inhibens DSM17395 and Ruegeria mobilis F1926 and TDA itself had no adverse effect on the target organisms. These results reaffirm TDA-producing Roseobacter bacteria as a promising group to be used as probiotics in aquaculture, whereas Actinobacteria, Pseudoalteromonas, Photobacteriaceae, and Vibrionaceae should be used with caution.

Vibrio anguillarum Is Genetically and Phenotypically Unaffected by Long-Term Continuous Exposure to the Antibacterial Compound Tropodithietic Acid

“…TDA is a broad-spectrum antibacterial that is bactericidal and inhibits the growth of several human and fish pathogens (16,(21)(22)(23) but has very low toxicity in Caenorhabditis elegans and Artemia (24). Recently, it was demonstrated that TDA is cytotoxic against N2a cells and OLN-93 cells of the mammalian nervous system and several cancer cell lines, respectively (25,26).…”

Biosynthesis of coral settlement cue tetrabromopyrrole in marine bacteria by a uniquely adapted brominase–thioesterase enzyme pair

“…In a recently discovered alternate route, the prolyl alpha-carboxyl carbon atom is lost during the biosynthesis of 1 and the cytotoxic marine bacterial natural product pentabromopseudilin (5, Fig. 1) (4,11). Uniquely, 5 is biosynthesized via the coupling of 2,3,4-tribromopyrrole (6, Fig.…”

“…natural products | biosynthesis | halogenation | enzymology M arine bacteria of the genus Pseudoalteromonas produce numerous small molecule natural products with varied roles in marine chemical ecology (1)(2)(3)(4). Recently, tetrabromopyrrole (1, Fig.…”

Unusual flavoenzyme catalysis in marine bacteria

“…While the participation of flavoenzymes as halogenating catalysts in chlorinated natural product biosynthesis is well established (Figure 2AB) [24], it is surprising to note that physiological marine brominating flavoenzymes, those that cannot catalyze the oxidative incorporation of chlorine [25], had evaded discovery until very recently. Querying the genetic and molecular bases for the biosynthesis of the cytotoxic [26] marine natural product pentabromopseudilin revealed the ‘ bmp ’ gene locus that incorporates two intriguing flavin-dependent brominases [27]. Of these, the enzyme Bmp2 catalyzes the tribromination of L-proline derived pyrrole ring that is acylated to an acyl carrier protein (ACP) (Figure 2C).…”