Differential effect of silver nanoparticles on the microbiome of adult and developing planaria.

Silver nanoparticles (AgNPs) are widely incorporated in household, consumer and medical products. Their unintentional release via wastewaters raises concerns on their environmental impact, particularly for aquatic organisms and their associated bacterial communities. It is known that the microbiome plays an important role in its host's health and physiology, e.g. by producing essential nutrients and providing protection against pathogens. A thorough understanding of the effects of AgNPs on bacterial communities and on their interactions with the host is crucial to fully assess AgNP toxicity on aquatic organisms. Our results indicate that the microbiome of the invertebrate Schmidtea mediterranea, a freshwater planarian, is affected by AgNP exposure at the tested 10 µg/ml concentration. Using targeted amplification of the bacterial 16S rRNA gene V3-V4 region, two independent experiments on the microbiomes of adult worms revealed a consistent decrease in Betaproteobacteriales after AgNP exposure, mainly attributed to a decrease in Curvibacter and Undibacterium. Although developing tissues and organisms are known to be more sensitive to toxic compounds, three independent experiments in regenerating worms showed a less pronounced effect of AgNP exposure on the microbiome, possibly because underlying bacterial community changes during development mask the AgNP induced effect. The presence of a polyvinyl-pyrrolidone (PVP) coating did not significantly alter the outcome of the experiments compared to those with uncoated particles. The observed variation between the different experiments underlines the highly variable nature of microbiomes and emphasises the need to repeat microbiome experiments, within and between physiological states of the animal.

High diversity of Vibrio spp. associated with different ecological niches in a marine aquaria system and description of Vibrio aquimaris sp. nov.

The aim of the study was to characterise the diversity and niche-specific colonization of Vibrio spp. in a marine aquaria system by a cultivation-dependent approach. A total of 53 Vibrio spp. isolates were cultured from different ecological niches in a marine aquarium including microplastic (MP) and sandy sediment particles (12 weeks after added sterile to the system), detritus, and the surrounding aquarium water. Based on the 16S rRNA gene sequence phylogeny and multilocus sequence analysis (MLSA) the isolates were assigned to seven different phylotypes. Six phylotypes were identified by high probability to the species level. The highest phylotype diversity was cultured from detritus and water (six out of seven phylotypes), while only two phylotypes were cultured from MP and sediment particles. Genomic fingerprinting indicated an even higher genetic diversity of Vibrio spp. at the strain (genotype) level. Again, the highest diversity of genotypes was recovered from detritus and water while only few partially particle-type specific genotypes were cultured from MP and sediment particles. Phylotype V-2 formed an independent branch in the MLSA tree and could not be assigned to a described Vibrio species. Isolates of this phylotype showed highest 16S rRNA gene sequence similarity to type strains of Vibrio japonicus (98.5%) and Vibrio caribbeanicus (98.4%). A representative isolate, strain THAF100T, was characterised by a polyphasic taxonomic approach and Vibrio aquimaris sp. nov., with strain THAF100T (=DSM 109633T=LMG 31434T=CIP 111709T) as type strain, is proposed as novel species.

Secondary Metabolites from Marine-Derived Fungi from China.

Marine-derived fungi play an important role in the search for structurally unique secondary metabolites, some of which show promising pharmacological activities that make them useful leads for drug discovery. Marine natural product research in China in general has made enormous progress in the last two decades as described in this chapter on fungal metabolites. This contribution covers 613 new natural products reported from 2001 to 2017 from marine-derived fungi obtained from algae, sponges, corals, and other marine organisms from Chinese waters. The genera Aspergillus (170 new natural products, 28%) and Penicillium (70 new natural products, 11%) were the main fungal producers of new natural products during the time period covered, whereas sponges (184 new natural products, 30%) were the most abundant source of new natural products, followed by corals (154 new natural products, 25%) and algae (130 new natural products, 21%). Close to 40% of all natural products covered in this contribution displayed various bioactivities. The major bioactivities reported were cytotoxicity against different cancer cell lines, antimicrobial (mainly antibacterial) activity, and antiviral activity, which accounted for 13%, 9%, and 3% of all natural products reported. In terms of structural classes, polyketides (188 new natural products, 31%) play a dominant role, and if prenylated polyketides and nitrogen-containing polyketides (included in meroterpenes and alkaloids in this contribution) are taken into account, their total number even exceeds 50%. Nitrogen-containing compounds including peptides (65 new natural products, 10%) and alkaloids (103 new natural products, 17%) are the second largest group.

Genomic taxonomy of the Mediterranei clade of the genus Vibrio (Gammaproteobacteria).

The first genomic study of Mediterranei clade using five type strains (V. mediterranei, V. maritimus, V. variabilis, V. thalassae, and V. barjaei) and fourteen reference strains isolated from marine organisms, seawater, water and sediments of the sea was performed. These bacterial strains were characterised by means of a polyphasic approach comprising 16S rRNA gene, multilocus sequence analysis (MLSA) of 139 single-copy genes, the DNA G + C content, ANI, and in silico phenotypic characterisation. We found that the species of the Mediterranei clade formed two separate clusters based in 16S rRNA gene sequence similarity, MLSA, OrthoANI, and Codon and Amino Acid usage. The Mediterranei clade species showed values between 76 and 95% for ANIb, 84 and 95% for ANIm. The core genome consisted of 2057 gene families and the pan-genome of 13,094 gene families. Based on the genomic analyses performed, the Mediterranei clade can be divided in two clusters, one with the strains of V. maritimus, V. variabilis and two potential new species, and the other cluster with the strains of V. mediterranei, V. thalassae, and V. barjaei.

Antifouling Properties of Dendritic Polyglycerols against Marine Macrofouling Organisms.

Dendritic polyglycerols (PGs) were synthesized and postmodified by grafting of poly(ethylene glycol) (PEG) and polypropylene glycol (PPG) diglycidyl ether groups, and their antifouling and fouling-release properties were tested. Coating characterization by spectroscopic ellipsometry, contact angle goniometry, attenuated total internal reflection-Fourier transform infrared spectroscopy (ATR-FTIR), and atomic force microscopy showed brushlike morphologies with a high degree of microscale roughness and the ability to absorb large amounts of water within seconds. PGs with three different thicknesses were tested in laboratory assays against settlement of larvae of the barnacle Balanus improvisus and against the settlement and removal of zoospores of the alga Ulva linza. Very low coating thicknesses, e.g., 11 nm, reduced the settlement of barnacles, under static conditions, to 2% compared with 55% for an octadecyltrichlorosilane reference surface. In contrast, zoospores of U. linza settled readily but the vast majority were removed by exposure to a shear force of 52 Pa. Both PEG and PPG modification increased the antifouling properties of the PG films, providing a direct comparison of the ultralow fouling properties of all three polymers. Both, the modified and the nonmodified PGs are promising components for incorporation into amphiphilic fouling-resistant coatings.

Cytotoxic Polyketides from the Marine Sponge-Derived Fungus Pestalotiopsis heterocornis XWS03F09.

Four new compounds, including two new polyketides, heterocornols M and N (1, 2), and a pair of epimers, heterocornols O and P (3, 4), were isolated from the fermentation broth of the marine sponge-derived fungus Pestalotiopsis heterocornis XWS03F09, together with three known compounds (5-7). The new chemical structures were established on the basis of a spectroscopic analysis, optical rotation, experimental and calculated electronic circular dichroism (ECD). All of the compounds (1-7) were evaluated for their cytotoxic activities, and heterocornols M-P (1-4) exhibited cytotoxicities against four human cancer cell lines with IC50 values of 20.4-94.2 µM.

Ottowia flava sp. nov., isolated from fish intestines.

A novel Gram-negative bacterium, non-motile and short rod-shaped, designated strain GY511T, was isolated from the intestines of fish collected from Maowei Sea, China. Growth occurred at pH 6.0-9.0 (optimum 7.0), 4-37 °C (optimum 28 °C) and at 0-2.5% (w/v) NaCl (optimum 1.0%). The result of 16S rRNA gene sequence analysis showed that strain GY511T is closely related to O. oryzae NBRC 113109T (97.6%), O. konkukae DSM 105395T (97.4%), Ottowia beijingensis CGMCC 1.12324T (95.9%), Ottowia pentelensis DSM 21699T (95.2%) and Ottowia thiooxydans DSM 14619T (95.0%). The DNA-DNA hybridization values of strain GY511T with O. oryzae NBRC 113109T and O. konkukae DSM 105395T were 35.4 ± 3.1% and 26.3 ± 1.8%, respectively. The major fatty acids (> 10%) were identified as summed feature 3 (C16:1ω7c and/or C16:1ω6c), C16:0 and summed feature 8 (C18:1ω7c and/or C18:1ω6c) and the major respiratory quinone was ubiquinone-8 (Q-8). The polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmethylethanolamine, two unidentified aminolipids and an unidentified phospholipid. The G+C content of the genomic DNA was 62.9 mol%. Thiosulfate could be utilized as co-substrate for aerobic growth and was oxidised to sulfate. On the basis of phenotypic, chemotaxonomic and molecular data, strain GY511T is considered to represent a novel species of the genus Ottowia, for which the name Ottowia flava sp. nov. is proposed. The type strain is GY511T (= NBRC 113500T = DSM 107425T = CGMCC 1.13650T).

Integrating Molecular Network and Culture Media Variation to Explore the Production of Bioactive Metabolites by Vibrio diabolicus A1SM3.

Vibrio diabolicus A1SM3 strain was isolated from a sediment sample from Manaure Solar Saltern in La Guajira and the produced crude extracts have shown antibacterial activity against methicillin-resistant Staphylococcus aureus and cytotoxic activity against human lung cell line. Thus, the aim of this research was to identify the main compound responsible for the biological activity observed and to systematically study how each carbon and nitrogen source in the growth media, and variation of the salinity, affect its production. For the characterization of the bioactive metabolites, 15 fractions obtained from Vibrio diabolicus A1SM3 crude extract were analyzed by HPLC-MS/MS and their activity was established. The bioactive fractions were dereplicated with Antibase and Marinlit databases, which combined with nuclear magnetic resonance (NMR) spectra and fragmentation by MS/MS, led to the identification of 2,2-di(3-indolyl)-3-indolone (isotrisindoline), an indole-derivative antibiotic, previously isolated from marine organisms. The influence of the variations of the culture media in isotrisindoline production was established by molecular network and MZmine showing that the media containing starch and peptone at 7% NaCl was the best culture media to produce it. Also, polyhydroxybutyrates (PHB) identification was established by MS/MS mainly in casamino acids media, contributing to the first report on PHB production by this strain.

Marine bacteria and fungi as promising source for new antibiotics.

Natural products and derivatives thereof are of considerable importance in the discovery of new pharmaceuticals, for example, for the treatment of cancer, diabetes, inflammation diseases, and infection diseases caused by bacteria, fungi, viruses, or parasites. The great biodiversity of marine microorganisms is reflected in their huge chemical diversity, which provides a rich source of biologically active compounds. An increasing interest in marine microorganisms as promising producers of new compounds with potential medical applications has raised increasing interest in the sustainable exploration of marine microbial resources for the discovery of new antibiotics, which is highlighted. The bottlenecks in the development of drugs using the large marine natural product pipeline are also discussed.

Neuroprotective Activity of Some Marine Fungal Metabolites in the 6-Hydroxydopamin- and Paraquat-Induced Parkinson's Disease Models.

A new melatonin analogue 6-hydroxy-N-acetyl-ß-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid (2) and 8-methoxy-3,5-dimethylisochroman-6-ol (3) from Penicillium sp. KMM 4672, candidusin A (4) and 4″-dehydroxycandidusin A (5) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide (6) from Aspergillus flocculosus, were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson's disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3″ and C-4″ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p-terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models.

Two Novel Aspochalasins from the Gut Fungus Aspergillus sp. Z4.

Two novel aspochalasins, tricochalasin A (1) and aspochalasin A2 (2), along with three known compounds (3⁻5) have been isolated from the different culture broth of Aspergillus sp., which was found in the gut of a marine isopod Ligia oceanica. Compound 1 contains a rare 5/6/6 tricyclic ring fused with the aspochalasin skeleton. The structures were determined on the basis of electrospray ionisation mass spectroscopy (ESIMS), nuclear magnetic resonance (NMR) spectral data, and the absolute configurations were further confirmed by modified Mosher's method. Cytotoxicity against the prostate cancer PC3 cell line were assayed by the MTT method. Compound 3 showed strong activity while the remaining compounds showed weak activity.

Prenylated Diphenyl Ethers from the Marine Algal-Derived Endophytic Fungus Aspergillus tennesseensis.

Considerable attention has been paid to marine derived endophytic fungi, owing to their capacity to produce novel secondary metabolites with potent bioactivities. In this study, two new compounds with a prenylated diphenyl ether structure-diorcinol L (1) and (R)-diorcinol B (2)-were isolated from the marine algal-derived endophytic fungus Aspergillus tennesseensis, along with seven known compounds: (S)-diorcinol B (3), 9-acetyldiorcinol B (4), diorcinol C (5), diorcinol D (6), diorcinol E (7), diorcinol J (8), and a dihydrobenzofuran derivative 9. Their structures were elucidated by extensive NMR spectroscopy studies. Compound 2 represents the first example of an R-configuration in the prenylated moiety. All these isolated compounds were examined for antimicrobial and cytotoxic activities. Compounds 1⁻9 exhibited antimicrobial activities against some human- and plant-pathogenic microbes with MIC values ranging from 2 to 64 µg/mL. Moreover, compound 9 displayed considerable inhibitory activity against the THP-1 cell line in vitro, with an IC50 value of 7.0 µg/mL.

New Cytotoxic Cyclic Peptide from the Marine Sponge-Associated Nocardiopsis sp. UR67.

A new cyclic hexapeptide, nocardiotide A (1), together with three known compounds-tryptophan (2), kynurenic acid (3), and 4-amino-3-methoxy benzoic acid (4)-were isolated and identified from the broth culture of Nocardiopsis sp. UR67 strain associated with the marine sponge Callyspongia sp. from the Red Sea. The structure elucidation of the isolated compounds were determined based on detailed spectroscopic data including ¹D and ²D nuclear magnetic resonance (NMR) experimental analyses in combination with high resolution electrospray ionization mass spectrometry (HR-ESI-MS), while the absolute stereochemistry of all amino acids components of nocardiotide A (1) was deduced using Marfey's method. Additionally, ten known metabolites were dereplicated using HR-ESI-MS analysis. Nocardiotide A (1) displayed significant cytotoxic effects towards the murine CT26 colon carcinoma, human HeLa cervix carcinoma, and human MM.1S multiple myeloma cell lines. The results obtained revealed sponge-associated Nocardiopsis as a substantial source of lead natural products with pronounced pharmacological activities.

Asperindoles A⁻D and a p-Terphenyl Derivative from the Ascidian-Derived Fungus Aspergillus sp. KMM 4676.

Four new indole-diterpene alkaloids asperindoles A⁻D (1⁻4) and the known p-terphenyl derivative 3″-hydroxyterphenyllin (5) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1⁻5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1⁻4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds. Asperindole A exhibits cytotoxic activity against hormone therapy-resistant PC-3 and 22Rv1, as well as hormone therapy-sensitive human prostate cancer cells, and induces apoptosis in these cells at low-micromolar concentrations.

Hoeflea prorocentri sp. nov., isolated from a culture of the marine dinoflagellate Prorocentrum mexicanum PM01.

A Gram-stain negative, aerobic, rod-shaped, non-motile, yellow-pigmented and non-spore-forming bacterial strain, designated PM5-8T, was isolated from a culture of a marine toxigenic dinoflagellate Prorocentrum mexicanum PM01. Strain PM5-8T grew at 15-35 °C (optimum, 25-30 °C) and pH 6-11 (optimum, 7.5-8). Cells required at least 1.5% (w/v) NaCl for growth, and can tolerate up to 7.0% with the optimum of 4%. Phylogenetic analysis based on 16S rRNA gene sequence revealed that the strain PM5-8T is closely related to members of the genus Hoeflea, with high sequence similarities with Hoeflea halophila JG120-1T (97.06%) and Hoeflea alexandrii AM1V30T (97.01%). DNA-DNA hybridization values between the isolate and other type strains of recognized species of the genus Hoeflea were between 11.8 and 25.2%, which is far below the value of 70% threshold for species delineation. The DNA G + C content was 50.3 mol%. The predominant cellular fatty acids of the strain were identified as summed feature 8 (C16:1 ω7c and/or C16:1 ω6c; 51.5%), C18:1 ω7c 11-methyl (20.7%), C16:0 (17.2%) and C18:0 (5.7%). The major respiratory quinone was Q-10. Polar lipids profiles contained phosphatidylcholine, phosphatidylglycerol, sulfoquinovosyl diacylglycerol, phosphatidylmono- methylethanolamine, phosphatidylethanolamine and four unidentified lipids. On the basis of the polyphasic taxonomic data presented, strain PM5-8T (= CCTCC AB 2016294T = KCTC 62490T) represents a novel species of the genus Hoeflea, for which the name Hoeflea prorocentri sp. nov. is proposed.

Atividade antimicrobiana e antibiofilme de nanopartículas de prata sobre isolados de Aeromonas spp. obtidos de organismos aquáticos / Antimicrobial and antibiofilm activity of silver nanoparticles against Aeromonas spp. isolated from aquatic organisms

O uso indiscriminado de antimicrobianos tem proporcionado a algumas bactérias patogênicas a seleção de cepas multirresistentes, situação que pode ser agravada pela formação do biofilme. Desta forma, as nanopartículas de prata (AgNPs) vêm se destacando como uma alternativa inovadora, de baixo custo e eficiente contra doenças causadas por bactérias. O objetivo deste estudo foi determinar a atividade antimicrobiana das AgNPs e a interferência na formação do biofilme de Aeromonas spp. obtidas de organismos aquáticos. As AgNPs foram sintetizadas quimicamente utilizando como agente redutor o citrato trissódico e caracterizadas por espectrofotometria ultravioleta-visível (UV-Vis). A atividade antimicrobiana foi realizada contra três isolados pelo método de microdiluição em caldo para determinar a concentração bactericida mínima (CBM) e um cultivo com CCCP, um inibidor da bomba de efluxo, foi realizado para complementar o efeito das AgNPs. A interferência no biofilme foi realizada segundo o protocolo de formação e consolidado, além da caracterização desta estrutura de resistência por microscopia eletrônica de varredura. No teste da CBM, as AgNPs não foram capazes de inativar o crescimento dos isolados, ao passo que o nitrato de prata obteve eficiência em diferentes concentrações. Na presença do inibidor de bomba de efluxo, dos isolados analisados, um passou de resistente a sensível na presença das nanopartículas. As AgNPs foram eficazes em diminuir a formação de biofilme, como também atuaram sobre o biofilme consolidado em todos os isolados testados. Estes resultados indicam o potencial das nanopartículas de prata em interferir com o biofilme de Aeromonas spp. de organismos aquáticos e seres humanos.(AU)

The indiscriminate use of antibiotics has selected some pathogenic bacteria being multidrug-resistant, a situation that can be exacerbated by biofilms formation. Thus, silver nanoparticles (AgNPs) have been highlighted as an innovative alternative, low-cost and effective against bacterial diseases. The aim of this study was to determine the antimicrobial activity of AgNPs and the interference in Aeromonas spp. biofilm formation. The strains were obtained from aquatic organisms. The AgNPs were chemically synthesized using as reducing agent trisodium citrate and characterized by ultraviolet-visible spectroscopy (UV-Vis). The antimicrobial activity was carried out against three isolates by the microdilution broth method for determining minimum bactericidal concentration (CBM) and cultivation of CCCP, an inhibitor of the efflux pump, was carried out to complement the effect of AgNPs. Interference in the biofilm formation was performed according to the protocol and consolidated, within the resistance structure characterization by scanning electron microscopy. In the test of the CBM, the AgNPs were unable to inactivate the growth of the isolates, while the silver nitrate obtained efficiency in different concentrations. In the efflux pump inhibitor presence the isolates were analyzed, one went from resistant to nanoparticles to sensitive. The AgNPs were effective in reducing of biofilm formation and acted on the consolidated biofilm in all tested isolates. These results indicate the silver nanoparticles to interfere with Aeromonas spp. biofilm from aquatic organisms and human bodies.(AU)

Anti-Inflammatory Effects of Curvularin-Type Metabolites from a Marine-Derived Fungal Strain Penicillium sp. SF-5859 in Lipopolysaccharide-Induced RAW264.7 Macrophages.

Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (2-9). The structures of these metabolites (1-9) were established by comprehensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). In vitro anti-inflammatory effects of these metabolites were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Among these metabolites, 3-9 were shown to strongly inhibit LPS-induced overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) with IC50 values ranging from 1.9 µM to 18.1 µM, and from 2.8 µM to 18.7 µM, respectively. In the further evaluation of signal pathways involved in these effects, the most active compound, (10E,15S)-10,11-dehydrocurvularin (8) attenuated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 macrophages. Furthermore, compound 8 was shown to suppress the upregulation of pro-inflammatory mediators and cytokines via the inhibition of the nuclear factor-κB (NF-κB) signaling pathway, but not through the mitogen-activated protein kinase (MAPK) pathway. Based on the comparisons of the different magnitude of the anti-inflammatory effects of these structurally-related metabolites, it was suggested that the opening of the 12-membered lactone ring in curvularin-type metabolites and blocking the phenol functionality led to the significant decrease in their anti-inflammatory activity.

Effect of pesticides on microbial communities in container aquatic habitats.

Container aquatic habitats support a specialized community of macroinvertebrates (e.g. mosquitoes) that feed on microbial communities associated with decaying organic matter. These aquatic habitats are often embedded within and around agricultural lands and are frequently exposed to pesticides. We used a microcosm approach to examine the single and combined effects of two herbicides (atrazine, glyphosate), and three insecticides (malathion, carbaryl, permethrin) on microbial communities of container aquatic habitats. MiSeq sequencing of the V4 region of both bacterial and archaeal 16S rRNA gene was used to characterize the microbial communities of indoor microcosms that were either exposed to each pesticide alone, a mix of herbicides, a mix of insecticides, or a mix of all five insecticides. Individual insecticides but not herbicides reduced the microbial diversity and richness and two insecticides, carbaryl and permethrin, also altered the microbial community structure. A mixture of herbicides had no effect on microbial diversity or structure but a mixture of insecticides or all five pesticides reduced microbial diversity and altered the community structure. These findings suggest that exposure of aquatic ecosystems to individual pesticides or their mixtures can disrupt aquatic microbial communities and there is need to decipher how these changes affect resident macroinvertebrate communities.

Antibiotic resistance genes detected in the marine sponge Petromica citrina from Brazilian coast

ABSTRACT Although antibiotic-resistant pathogens pose a significant threat to human health, the environmental reservoirs of the resistance determinants are still poorly understood. This study reports the detection of resistance genes (ermB, mecA, mupA, qnrA, qnrB and tetL) to antibiotics among certain culturable and unculturable bacteria associated with the marine sponge Petromica citrina. The antimicrobial activities elicited by P. citrina and its associated bacteria are also described. The results indicate that the marine environment could play an important role in the development of antibiotic resistance and the dissemination of resistance genes among bacteria.

Suppressive effects of three diketopiperazines from marine-derived bacteria on polyphosphate-mediated septic responses.

Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bioactivities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of diketopiperazine and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Diketopiperazine suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, diketopiperazine demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of diketopiperazine on various systemic inflammatory diseases, such as sepsis or septic shock.