Nigribactin, a Novel Siderophore from Vibrio nigripulchritudo, Modulates Staphylococcus aureus Virulence Gene Expression

Nielsen, Anita Kildebæk; Månsson, Maria; Wietz, Matthias; Varming, Anders K.; Phipps, Richard Kerry; Larsen, Thomas Ostenfeld; Gram, Lone; Ingmer, Hanne

doi:10.3390/md10112584

Cited by 22 publications

(22 citation statements)

References 29 publications

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“…4). Siderophores similar to fluvibactin can inhibit bacterial and fungal growth (20,56), and catechol iron chelators have also been suggested to protect bacteria from oxidative stress (57,58). Hence, beside the competitive advantage during surface colonization due to the antibacterial activity of fluvibactin, producers of this compound might as well be protected from oxidative stress, which is a prevalent phenomenon in the marine environment (59).…”

Section: Discussionmentioning

confidence: 99%

“…During rescreening, only 39 strains retained their antagonistic activity (18). We isolated the potent antibiotics holomycin and andrimid from Vibrio coralliilyticus and Photobacterium galatheae, respectively (9,18), as well as modulators of virulence in Staphylococcus aureus, such as ngercheumicins F, G, H, and I (19), nigribactin (20), and solonamide B (21). However, we were challenged by the marked reduction in bioactivity during rescreening.…”

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confidence: 99%

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Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

Giubergia

Phippen

Gotfredsen

et al. 2016

Appl Environ Microbiol

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Many factors, such as the substrate and the growth phase, influence biosynthesis of secondary metabolites in microorganisms. Therefore, it is crucial to consider these factors when establishing a bioprospecting strategy. Mimicking the conditions of the natural environment has been suggested as a means of inducing or influencing microbial secondary metabolite production. The purpose of the present study was to determine how the bioactivity of Vibrionaceae was influenced by carbon sources typical of their natural environment. We determined how mannose and chitin, compared to glucose, influenced the antibacterial activity of a collection of Vibrionaceae strains isolated because of their ability to produce antibacterial compounds but that in subsequent screenings seemed to have lost this ability. The numbers of bioactive isolates were 2-and 3.5-fold higher when strains were grown on mannose and chitin, respectively, than on glucose. As secondary metabolites are typically produced during late growth, potential producers were also allowed 1 to 2 days of growth before exposure to the pathogen. This strategy led to a 3-fold increase in the number of bioactive strains on glucose and an 8-fold increase on both chitin and mannose. We selected two bioactive strains belonging to species for which antibacterial activity had not previously been identified. Using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry and bioassay-guided fractionation, we found that the siderophore fluvibactin was responsible for the antibacterial activity of Vibrio furnissii and Vibrio fluvialis. These results suggest a role of chitin in the regulation of secondary metabolism in vibrios and demonstrate that considering bacterial ecophysiology during development of screening strategies will facilitate bioprospecting. IMPORTANCEA challenge in microbial natural product discovery is the elicitation of the biosynthetic gene clusters that are silent when microorganisms are grown under standard laboratory conditions. We hypothesized that, since the clusters are not lost during proliferation in the natural niche of the microorganisms, they must, under such conditions, be functional. Here, we demonstrate that an ecology-based approach in which the producer organism is allowed a temporal advantage and where growth conditions are mimicking the natural niche remarkably increases the number of Vibrionaceae strains producing antibacterial compounds.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

Giubergia

Phippen

Gotfredsen

et al. 2016

Appl Environ Microbiol

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“…nigripulchritudo)(65), fluvibactin (Vibrio fluvialis)(66), vibriobactin (V. cholerae)(19), photobactin [Photorhabdus spp (21). and S. plymuthica V4 (this study)], serratiochelin (Serratia spp.…”

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confidence: 72%

Natural combinatorial genetics and prolific polyamine production enable siderophore diversification in Serratia plymuthica

Cleto

Haslinger

Prather

et al. 2020

Preprint

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AbstractSiderophores are small molecules with unmatched capacity to scavenge iron from proteins and the extracellular milieu, where it mostly occurs as insoluble Fe3+. Siderophores chelate Fe3+ for uptake into the cell, where it is reduced to soluble Fe2+. As iron is essential for bacterial survival, siderophores are key molecules in low soluble iron conditions. Bacteria have devised many strategies to synthesize proprietary siderophores to avoid siderophore piracy by competing organisms, e.g., by incorporating different polyamine backbones into siderophores, while maintaining the catechol moieties. We report that Serratia plymuthica V4 produces a variety of siderophores, which we term the siderome, and which are assembled by the concerted action of enzymes encoded in two independent gene clusters. Besides assembling serratiochelin with diaminopropane, S. plymuthica utilizes putrescine and the same set of enzymes to assemble photobactin, a siderophore described for Photorhabdus luminescens. The enzymes encoded by one of the gene clusters can independently assemble enterobactin. A third, independent operon is responsible for biosynthesis of the hydroxamate siderophore aerobactin, initially described in Enterobacter aerogenes. Mutant strains not synthesizing polyamine-siderophores significantly increased enterobactin production levels, though lack of enterobactin did not impact serratiochelin production. Knocking out SchF0, an enzyme involved in the assembly of enterobactin alone, significantly reduced bacterial fitness. This study illuminates the interplay between siderophore biosynthetic pathways and polyamine production superpathways, indicating routes of molecular diversification. Given its natural yields of diaminopropane (97.75 μmol/g DW) and putrescine (30.83 μmol/g DW), S. plymuthica can be exploited for the industrial production of these compounds.Significance StatementSiderophores are molecules crucial for bacterial survival in low iron environments. Bacteria have evolved the capacity to pirate siderophores made by other bacterial strains and to diversify the structure of their own siderophores, to prevent piracy. We found that Serratia plymuthica V4 produces five different siderophores using three gene clusters and a polyamine production superpathway. The most well studied siderophore, enterobactin, rather than the strain’s proprietary and by far most abundant siderophore, serratiochelin, displayed a crucial role in the fitness of S. plymuthica. Our results also indicate that this strain is a good candidate for engineering the large-scale production of diaminopropane (DAP), as without any optimization it produced the highest amounts of DAP reported for wild-type strains.

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“…or potentially toxic (e.g., V. nigripulchritudo). Nevertheless, their secondary metabolites provide them with the capability to regulate bacterial virulence expression (20) and kill bacteria (18), algae causing harmful algal blooms (HAB) (40), parasites (41), or tumor cells (55). These bacteria could therefore have value, e.g., as control agents of biofouling and HAB in the marine environment, as producers of cancer treatment compounds, or as antibacterial or antiparasitic agents.…”

Section: Discussionmentioning

confidence: 99%

“…and C. elegans. The antibacterial activity of V. nigripulchritudo is linked to the production of the siderophore nigribactin (20). Siderophores are iron-chelating compounds, which have been related to virulence in bacterial pathogens.…”

Section: Discussionmentioning

confidence: 99%

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

Neu

Månsson

Gram

et al. 2014

Appl Environ Microbiol

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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.

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Nigribactin, a Novel Siderophore from Vibrio nigripulchritudo, Modulates Staphylococcus aureus Virulence Gene Expression

Cited by 22 publications

References 29 publications

Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae

Natural combinatorial genetics and prolific polyamine production enable siderophore diversification in Serratia plymuthica

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

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