William G.L. Aalbersberg

Marine actinomycetes: an ongoing source of novel bioactive metabolites

Actinomycetes are virtually unlimited sources of novel compounds with many therapeutic applications and hold a prominent position due to their diversity and proven ability to produce novel bioactive compounds. There are more than 22,000 known microbial secondary metabolites, 70% of which are produced by actinomycetes, 20% from fungi, 7% from Bacillus spp. and 1-2% by other bacteria. Among the actinomycetes, streptomycetes group are considered economically important because out of the approximately more than 10,000 known antibiotics, 50-55% are produced by this genus. The ecological role of actinomycetes in the marine ecosystem is largely neglected and various assumptions meant there was little incentive to isolate marine strains for search and discovery of new drugs. The search for and discovery of rare and new actinomycetes is of significant interest to drug discovery due to a growing need for the development of new and potent therapeutic agents. Modern molecular technologies are adding strength to the target-directed search for detection and isolation of bioactive actinomycetes, and continued development of improved cultivation methods and molecular technologies for accessing the marine environment promises to provide access to this significant new source of chemical diversity with novel/rare actinomycetes including new species of previously reported actinomycetes.

Further analyses on Micronesian banana, taro, breadfruit and other foods for provitamin A carotenoids and minerals

Few Micronesian foods have been analyzed for nutrient content. Information is needed on locally grown, culturally acceptable foods that could be promoted to alleviate, vitamin A deficiency in the Federated States of Micronesia. Using an ethnographic approach that included key informant interviews and observation, Micronesian cultivars with potential for high-carotenoid content according to their coloration were identified. These cultivars of banana, giant swamp taro, breadfruit and other foods were analyzed for alpha- and beta-carotene using high-performance liquid chromatography (HPLC) and for nine minerals using inductively coupled plasma (ICP). A wide range of provitamin A carotenoid levels was found in banana, taro, and breadfruit cultivars, some containing very high levels (beta-carotene content from 515 to 6360 mug/100 g in banana, 260 to 1651 mug/100 g in taro, and 295 to 868 mug/100 g in breadfruit, edible portion). Other cultivars contained moderate levels, but as they can be eaten in large quantities, they may contribute significantly to vitamin A status. The taro samples contained very high levels of zinc (mean 5.9 mg/100 g) and significant levels of other minerals (mean content of calcium was 120 mg/100 g). These staples with cultural acceptability and high availability potentially could play a role in vitamin A, micronutrient, and chronic disease programs in the Pacific

Naseseazines A and B: A New Dimeric Diketopiperazine Framework from a Marine-Derived Actinomycete, Streptomyces sp.

Chemical analysis of a Streptomyces sp. (CMB-MQ030) isolated from a Fijian marine sediment yielded two new diketopiperazines, naseseazines A and B (1, 2), featuring a new dimeric framework. Structures were determined by detailed spectroscopic analysis and C(3) Marfeys analysis.

Correspondence between human diet, body composition and stable isotopic composition of hair and breath in Fijian villagers

The main aim of this work was to describe the relationship between diet, and hair and breath isotopic composition. From one Fijian rural village, hair and breath samples were procured from 20 women. Physical anthropometrics were made, and hair 13C/12C and 15N/14N and breath 13C/12C were measured. Individual diet diaries were kept for two of the four preceding weeks, and isotopic compositions of items which accounted for most of the diet were measured. Individual average diets were analysed for macronutrient and energy content and conform to reasonable nutritional expectation. Characteristics of the diet are described in terms of protein and energy, their patterning with respect to different clusters of food items and their relationship to individuals’ anthropometry. Breath CO2 is depleted in 13C by 1–2‰ on average with respect to the total diet. Hair was enriched on average by 4.1‰ in nitrogen and 4.5‰ in carbon with respect to the total diet. There was insufficient population variation in hair isotopic composition to establish individual hair–diet isotopic differences. The definite relationship that we establish in this work, between dietary and tissue isotopic values for a human community, provides a basis for determining and validating dietary regimes more generally within non-industrial, non-global-‘supermarket’ economies.

High content live cell imaging for the discovery of new antimalarial marine natural products

BackgroundThe human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum.MethodsA high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope.ResultsImage analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasites phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts.ConclusionCollectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials.

Antimalarial Bromophycolides J-Q from the Fijian Red Alga Callophycus serratus

Bromophycolides J-Q (1-8) were isolated from extracts of the Fijian red alga Callophycus serratus and identified with 1D and 2D NMR spectroscopy and mass spectral analyses. These diterpene-benzoate macrolides represent two novel carbon skeletons and add to the 10 previously reported bromophycolides (9-18) from this alga. Among these 18 bromophycolides, several exhibited activities in the low micromolar range against the human malaria parasite Plasmodium falciparum.

Bioactive Bromophycolides R−U from the Fijian Red Alga Callophycus serratus

Four new bromophycolides, R-U (1-4), were isolated from the Fijian red alga Callophycus serratus and were identified by 1D and 2D NMR and mass spectroscopic analyses. These compounds expand the known structural variety of diterpene-benzoate macrolides and exhibited modest cytotoxicity toward selected human cancer cell lines. Bromophycolide S (2) also showed submicromolar activity against the human malaria parasite Plasmodium falciparum.

Carotenoid and vitamin content of Karat and other Micronesian banana cultivars

We previously found high carotenoid levels in Karat and other Micronesian bananas, indicating potential importance for alleviating vitamin A deficiency and other nutritionally related health problems in the Federated States of Micronesia. Past work focused on carotenoid and mineral analyses, whereas here we investigated 16 cultivars (most not previously analysed) for a broader micronutrient profile, including seven vitamins. Karat carotenoid levels were higher than in previous analyses, confirming Karat as exceptionally carotenoid-rich. We identified an additional 10 carotenoid-rich cultivars, expanding the range having potential for alleviating vitamin A deficiency. A striking finding is the high riboflavin level in Karat, including high levels of uncharacterized flavonoids. Niacin and α-tocopherol are at levels that may contribute importantly to dietary intake within normal patterns of consumption. These data present a more complete basis for promoting the nutritional benefits of these banana cultivars where they are consumed in the Pacific, and potential benefits for promoting elsewhere.

Small islands, valuable insights: systems of customary resource use and resilience to climate change in the Pacific

Understanding how social-ecological systems are and can be resilient to climate change is one of the worlds most crucial problems today. It requires knowledge at local and global scales, the integration of natural and social sciences, and a focus on biocultural diversity. Small Pacific Islands and the knowledge-practice-belief systems of their peoples have a long history of resilience to environmental variability and unpredictability, including in areas with marginal habitats and with periodic, severe disturbance (e.g., drought, flood, storms, and tsunami). We review the state of research on these knowledge systems as it pertains to resilience and adaptation, and we highlight critical research needs to address the interrelated areas of: (1) local-scale expertise and observations of change with regard to weather, life-history cycles, and ecological processes; (2) customary resource management institutions and practices (i.e., with agroforests and the nearshore marine environment); and (3) the roles of leaders, social institutions, and social networks in the context of disturbance and change. We conclude that these knowledge systems can contribute high-resolution observations, benchmark data, and insights into practices that enhance resilience and adaptive capacity in integrated terrestrial and marine systems. Community-based and participatory approaches can complement and ground-truth climate models and direct culturally appropriate resource management, research, and adaptation measures. Although most islands in the Pacific are small, their knowledge systems include valuable insights on seasonal cycles, ecological processes, and the management of biocultural diversity that are relevant at a broad scale for understanding resilience and adaptability to the social-ecological effects of climate change.

Isolation and identification of a potent antimalarial and antibacterial polyacetylene from Bidens pilosa.

Diseases caused by malaria parasites and pathogenic bacteria were thought to be on the brink of eradication in the 1950-1960s, but they have once again become a serious threat to mankind as a result of the appearance of multidrug resistant strains. The spread of these multidrug resistant organisms has prompted a worldwide search for new classes of effective antimalarial and antibacterial drugs. Natural products have been recognized as highly important candidates for this purpose. Our attention has focused on the herbal plant Bidens pilosa, a weed common throughout the world, as one of the target plants in the search for new active compounds, owing to its empirical use in the treatment of infectious diseases and to pharmaco-chemical studies of its crude extract. We report the isolation of two new compounds of B. pilosa, the linear polyacetylenic diol 1 and its glucoside 2 which have previously been isolated from different plants. Compound 1 exhibited highly potent antimalarial and antibacterial properties in vitro as well as potent antimalarial activity by way of intravenous injection in vivo, thereby representing a promising new class of drugs potentially effective in the treatment of malarial and bacterial diseases. We suspect that discovery of these compounds in B. pilosa in appreciable quantity is because the Fijian tradition of using the fresh plant for extraction rather than the Asian tradition of using dried plants (1 is unstable in the dried state) was followed.