Isolation and Biological Evaluation of 8-<i>epi</i>-Malyngamide C from the Floridian Marine Cyanobacterium <i>Lyngbya majuscula</i>

Kwan, Jason C.; Teplitski, Max; Gunasekera, Sarath P.; Paul, Valerie J.; Luesch, Hendrik

doi:10.1021/np900614n

Cited by 79 publications

(72 citation statements)

References 33 publications

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“…It was identified based on the HRMS data (HRESI/APCIMS m/z 257.2127 [M+H] + (calculated for C 15 H 29 O 3 , 257.2117)) and was further confirmed by comparing the 1 H nuclear magnetic resonance spectroscopy data with an authentic sample of lyngbic acid previously isolated from other benthic filamentous marine cyanobacteria. Lyngbic acid extracted from BBD gave a specific rotation value of [α] 25 D − 12.0 (c 0.06, CHCl 3 ; Supplementary Figure S7), similar to the specific rotation value of lyngbic acid reported earlier from other cyanobacteria [α] 26 D − 9 (c 7.3, CHCl 3 ) (Cardellina et al, 1978); [α] 20 D − 12.6 (c 0.8, CH 3 OH) (Kwan et al, 2010). When BBD mats were collected in quantities that were suitable for chemical extractions and subsequent analyses, the presence of lyngbic acid in BBD samples was ascertained by nuclear magnetic resonance spectroscopy and/or HRMS.…”

Section: Lyngbic Acid Is Abundant Within Bbdsupporting

confidence: 79%

“…A portion (0.004 g) of the subfraction 4 (0.023 g), eluted with MeOH-H 2 O (4:1), was further separated by reversed-phase HPLC using the same conditions to give 0.9 mg of lyngbic acid (yield 0.10% dry wt, 4.1% of EtOAc-soluble fraction). The structure of lyngbic acid was determined using the proton nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry and optical rotation data and confirmed by comparison with published data and data from our previously isolated samples of lyngbic acid (Cardellina et al, 1978;Kwan et al, 2010;Soares et al, 2015). The presence of lyngbic acid in other collections of BBD (Belize: 1 March 2013; FL Keys: Looe Key 17 May 2013, 12 September 2013, 20 November 2013; and Wonderland Reef 10 June 2013) was determined by identifying the presence of the key methoxy and unsaturation proton signals in the nuclear magnetic resonance spectroscopy spectra of the extracts and fractions.…”

Section: Isolation Of Lyngbic Acidsupporting

confidence: 53%

“…Therefore, functions of the cyanobacterial metabolite lyngbic acid may include manipulation of these behaviors to control interactions within BBD and its interactions with the host coral. This fundamental role for lyngbic acid as a QS inhibitor against vibrios may also explain its presence in so many different benthic filamentous marine cyanobacteria (Cardellina et al, 1978;Kwan et al, 2010;Soares et al, 2015).…”

Section: Discussionmentioning

confidence: 95%

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Microbiome shifts and the inhibition of quorum sensing by Black Band Disease cyanobacteria

et al. 2015

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Disruption of the microbiome often correlates with the appearance of disease symptoms in metaorganisms such as corals. In Black Band Disease (BBD), a polymicrobial disease consortium dominated by the filamentous cyanobacterium Roseofilum reptotaenium displaces members of the epibiotic microbiome. We examined both normal surface microbiomes and BBD consortia on Caribbean corals and found that the microbiomes of healthy corals were dominated by Gammaproteobacteria, in particular Halomonas spp., and were remarkably stable across spatial and temporal scales. In contrast, the microbial community structure in black band consortia was more variable and more diverse. Nevertheless, deep sequencing revealed that members of the disease consortium were present in every sampled surface microbiome of Montastraea, Orbicella and Pseudodiploria corals, regardless of the health status. Within the BBD consortium, we identified lyngbic acid, a cyanobacterial secondary metabolite. It strongly inhibited quorum sensing (QS) in the Vibrio harveyi QS reporters. The effects of lyngbic acid on the QS reporters depended on the presence of the CAI-1 receptor CqsS. Lyngbic acid inhibited luminescence in native coral Vibrio spp. that also possess the CAI-1-mediated QS. The effects of this naturally occurring QS inhibitor on bacterial regulatory networks potentially contribute to the structuring of the interactions within BBD consortia.

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Section: Lyngbic Acid Is Abundant Within Bbdsupporting

confidence: 79%

Section: Isolation Of Lyngbic Acidsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 95%

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Microbiome shifts and the inhibition of quorum sensing by Black Band Disease cyanobacteria

et al. 2015

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“…One of the common biological roles of fatty acid compounds produced by bacteria in large quantities is the interference with quorum sensing (communication between bacteria in response to high population densities). This was shown in several previous reports, [17][18][19][20] including by our group where we reported the anti-quorum sensing activity of lyngbyoic acid. 21 In Pseudomonas aeruginosa, quorum sensing (QS) system integrates two chemically distinct classes of signal molecules which act on differnet QS pathways, the Nacylhomoserine lactones which act on the LasR-LasI pathway, and the 4-quinolones which act on the Pseudomonas quinolone signaling pathway.…”

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confidence: 83%

Modular Strategies for Structure and Function Employed by Marine Cyanobacteria: Characterization and Synthesis of Pitinoic Acids

Montaser¹,

Paul²,

Luesch³

2013

Planta Med

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Novel bioactive lipids were identified from a Guamanian cyanobacterium; the Pseudomonas aeruginosa quorum sensing inhibitor pitinoic acid A (1) and the anti-inflammatory pitinoic acids B (2) and C. The structure of 2 was confirmed by synthesis, which also allowed for biological evaluation. Since 2 is an ester of pitinoic acids A and C, it represents a prodrug strategy to liberate dual biological activity for the management of P. aeruginosa infections and their associated inflammation.Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic infections in different host tissues and organs. For example, cystic fibrosis (CF) infections and microbial keratitis (MK) are two of the most serious lung and eye infections, respectively, caused by this organism. 1, 2 Bacterial quorum sensing (QS) has been shown to play a major role in bacterial pathogenesis, where the infection and tissue destruction are facilitated by several QS-regulated virulence factors including elastase (LasB) and the pigment pyocyanin. 2,3 Tissue damage is also aggravated by the host's defense response, where the release of pro-inflammatory mediators and the prolonged inflammatory response are other contributors to tissue pathology. 2, 4-8 Accordingly, inhibiting QS pathways in P. aeruginosa and simultaneously controlling the associated inflammatory response is a promising strategy for the treatment of infections caused by this organism.luesch@cop.ufl.edu. Supporting Information Available. 1D and 2D NMR spectra for compounds 1 and 2, supporting figures including spectral data and characterization of synthetic intermediates, experimental procedures and additional RT-qPCR data. This material is available free of charge via the Internet at http://pubs.acs.org. During our efforts to discover novel bioactive compounds from marine cyanobacteria, we explored a population of a marine cyanobacterium morphologically similar to Lyngbya sp. NIH Public Accesscollected from a channel at the north end of Piti Bay at Guam, through NMR-guided fractionation. We isolated and characterized the novel lipids pitinoic acid A (1) (5-methylene decanoic acid) and its chlorinated ester, pitinoic acid B (2). The fatty acid 1 inhibits QS in P. aeruginosa, while the ester 2 prevents the induction of pro-inflammatory cytokine expression in LPS-induced THP-1 macrophages. In addition, we were able to identify the presence of pitinoic acid C, the alcohol moiety in 2, in one HPLC-fraction, which also maintained the anti-inflammatory effect detected for 2. Based on this, 2 appears to be a nature-designed prodrug which could deliver two essential moieties with different bioactivities upon hydrolysis; the QS-inhibitory module pitinoic acid A (1) and the antiinflammatory module pitinoic acid C.The EtOAc-MeOH extract was subjected to solvent-solvent partitioning followed by fractionation using silica gel chromatography. 1 H NMR profiles of the generated silica fractions showed a major simple fatty acid (1) HPLC purification of another silica fraction that elut...

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“…The ability of marine prokaryotes and eukaryotes to excrete compounds that stimulate or inhibit QS reporters is now well documented (Pasmore and Costerton, 2003;Wagner-Dobler et al, 2005;Skindersoe et al, 2008;Teasdale et al, 2009;Kwan et al, 2010); however, ecological roles of these compounds and of the bacteria that produce them are less understood. Therefore, our subsequent experiments focused on testing the behaviors of the isolates in the dual-species microbial consortia consisting of the coral pathogen S. marcescens PDL100 and the isolate of interest.…”

Section: Effect On Swarming In Serratia Marcescensmentioning

confidence: 99%

Signaling-mediated cross-talk modulates swarming and biofilm formation in a coral pathogen Serratia marcescens

et al. 2011

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Interactions within microbial communities associated with marine holobionts contribute importantly to the health of these symbiotic organisms formed by invertebrates, dinoflagellates and bacteria. However, mechanisms that control invertebrate-associated microbiota are not yet fully understood. Hydrophobic compounds that were isolated from surfaces of asymptomatic corals inhibited biofilm formation by the white pox pathogen Serratia marcescens PDL100, indicating that signals capable of affecting the associated microbiota are produced in situ. However, neither the origin nor structures of these signals are currently known. A functional survey of bacteria recovered from coral mucus and from cultures of the dinoflagellate Symbiodinium spp. revealed that they could alter swarming and biofilm formation in S. marcescens. As swarming and biofilm formation are inversely regulated, the ability of some native a-proteobacteria to affect both behaviors suggests that the a-proteobacterial signal(s) target a global regulatory switch controlling the behaviors in the pathogen. Isolates of Marinobacter sp. inhibited both biofilm formation and swarming in S. marcescens PDL100, without affecting growth of the coral pathogen, indicative of the production of multiple inhibitors, likely targeting lower level regulatory genes or functions. A multi-species cocktail containing these strains inhibited progression of a disease caused by S. marcescens in a model polyp Aiptasia pallida. An a-proteobacterial isolate 44B9 had a similar effect. Even though B4% of native holobiont-associated bacteria produced compounds capable of triggering responses in well-characterized N-acyl homoserine lactone (AHL) biosensors, there was no strong correlation between the production of AHL-like signals and disruption of biofilms or swarming in S. marcescens.

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Isolation and Biological Evaluation of 8-epi-Malyngamide C from the Floridian Marine Cyanobacterium Lyngbya majuscula

Cited by 79 publications

References 33 publications

Microbiome shifts and the inhibition of quorum sensing by Black Band Disease cyanobacteria

Microbiome shifts and the inhibition of quorum sensing by Black Band Disease cyanobacteria

Modular Strategies for Structure and Function Employed by Marine Cyanobacteria: Characterization and Synthesis of Pitinoic Acids

Signaling-mediated cross-talk modulates swarming and biofilm formation in a coral pathogen Serratia marcescens

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