Impact of Marine Chemical Ecology Research on the Discovery and Development of New Pharmaceuticals.

Diverse ecologically important metabolites, such as allelochemicals, infochemicals and volatile organic chemicals, are involved in marine organismal interactions. Chemically mediated interactions between intra- and interspecific organisms can have a significant impact on community organization, population structure and ecosystem functioning. Advances in analytical techniques, microscopy and genomics are providing insights on the chemistry and functional roles of the metabolites involved in such interactions. This review highlights the targeted translational value of several marine chemical ecology-driven research studies and their impact on the sustainable discovery of novel therapeutic agents. These chemical ecology-based approaches include activated defense, allelochemicals arising from organismal interactions, spatio-temporal variations of allelochemicals and phylogeny-based approaches. In addition, innovative analytical techniques used in the mapping of surface metabolites as well as in metabolite translocation within marine holobionts are summarized. Chemical information related to the maintenance of the marine symbioses and biosyntheses of specialized compounds can be harnessed for biomedical applications, particularly in microbial fermentation and compound production. Furthermore, the impact of climate change on the chemical ecology of marine organisms-especially on the production, functionality and perception of allelochemicals-and its implications on drug discovery efforts will be presented.

Becoming nose-blind-Climate change impacts on chemical communication.

Chemical communication via infochemicals plays a pivotal role in ecological interactions, allowing organisms to sense their environment, locate predators, food, habitats, or mates. A growing number of studies suggest that climate change-associated stressors can modify these chemically mediated interactions, causing info-disruption that scales up to the ecosystem level. However, our understanding of the underlying mechanisms is scarce. Evidenced by a range of examples, we illustrate in this opinion piece that climate change affects different realms in similar patterns, from molecular to ecosystem-wide levels. We assess the importance of different stressors for terrestrial, freshwater, and marine ecosystems and propose a systematic approach to address highlighted knowledge gaps and cross-disciplinary research avenues.

Co-culturing microbial consortia: approaches for applications in biomanufacturing and bioprocessing.

The application of microbial co-cultures is now recognized in the fields of biotechnology, ecology, and medicine. Understanding the biological interactions that govern the association of microorganisms would shape the way in which artificial/synthetic co-cultures or consortia are developed. The ability to accurately predict and control cell-to-cell interactions fully would be a significant enabler in synthetic biology. Co-culturing method development holds the key to strategically engineer environments in which the co-cultured microorganism can be monitored. Various approaches have been employed which aim to emulate the natural environment and gain access to the untapped natural resources emerging from cross-talk between partners. Amongst these methods are the use of a communal liquid medium for growth, use of a solid-liquid interface, membrane separation, spatial separation, and use of microfluidics systems. Maximizing the information content of interactions monitored is one of the major challenges that needs to be addressed by these designs. This review critically evaluates the significance and drawbacks of the co-culturing approaches used to this day in biotechnological applications, relevant to biomanufacturing. It is recommended that experimental results for a co-cultured species should be validated with different co-culture approaches due to variations in interactions that could exist as a result of the culturing method selected.

Compression principle and Zipf's Law of brevity in infochemical communication.

Compression has been presented as a general principle of animal communication. Zipf's Law of brevity is a manifestation of this postulate and can be generalized as the tendency of more frequent communicative elements to be shorter. Previous works supported this claim, showing evidence of Zipf's Law of brevity in animal acoustical communication and human language. However, a significant part of the communicative effort in biological systems is carried out in other transmission channels, such as those based on infochemicals. To fill this gap, we seek, for the first time, evidence of this principle in infochemical communication by analysing the statistical tendency of more frequent infochemicals to be chemically shorter and lighter. We analyse data from the largest and most comprehensive open-access infochemical database known as Pherobase, recovering Zipf's Law of brevity in interspecific communication (allelochemicals) but not in intraspecific communication (pheromones). Moreover, these results are robust even when addressing different magnitudes of study or mathematical approaches. Therefore, different dynamics from the compression principle would dominate intraspecific chemical communication, defying the universality of Zipf's Law of brevity. To conclude, we discuss the exception found for pheromones in the light of other potential communicative paradigms such as pressures on successful communication or the Handicap principle.

Parasitic wasps avoid ant-protected hemipteran hosts via the detection of ant cuticular hydrocarbons.

One of the most studied and best-known mutualistic relationships between insects is that between ants and phloem-feeding insects. Ants feed on honeydew excreted by phloem-feeding insects and, in exchange, attack the phloem feeders' natural enemies, including parasitic wasps. However, parasitic wasps are under selection to exploit information on hazards and avoid them. Here, we tested whether parasitic wasps detect the previous presence of ants attending colonies of phloem feeders. Behavioural assays demonstrate that wasps left colonies previously attended by ants more frequently than control colonies. This behaviour has a potential cost for the parasitic wasp as females inserted their ovipositor in fewer hosts per colony. In a further bioassay, wasps spent less time on papers impregnated with extracts of the ant cues than on control papers. Gas chromatography coupled with mass spectrometry analyses demonstrated that ants left a blend of cuticular hydrocarbons when they attended colonies of phloem feeders. These cuticular hydrocarbons are deposited passively when ants search for food. Overall, these results suggest, for the first time, that parasitic wasps of honeydew producers detect the previous presence of mutualistic ants through contact infochemicals. We anticipate such interactions to be widespread and to have implications in numerous ecosystems, as phloem feeders are usually tended by ants.

Infochemicals in terrestrial plants and seaweed holobionts: current and future trends.

Since the holobiont concept came into the limelight ten years ago, we have become aware that responses of holobionts to climate change stressors may be driven by shifts in the microbiota. However, the complex interactions underlying holobiont responses across aquatic and terrestrial ecosystems remain largely unresolved. One of the key factors driving these responses is the infochemical-mediated communication in the holobiont. In order to come up with a holistic picture, in this Viewpoint we compare mechanisms and infochemicals in the rhizosphere of plants and the eco-chemosphere of seaweeds in response to climate change stressors and other environmental stressors, including drought, warming and nutrient stress. Furthermore, we discuss the inclusion of chemical ecology concepts that are of crucial importance in driving holobiont survival, adaptation and/or holobiont breakdown. Infochemicals can thus be regarded as a 'missing link' in our understanding of holobiont response to climate change and should be investigated while investigating the responses of plant and seaweed holobionts to climate change. This will set the basis for improving our understanding of holobiont responses to climate change stressors across terrestrial and aquatic ecosystems.

Symbioses of Cyanobacteria in Marine Environments: Ecological Insights and Biotechnological Perspectives.

Cyanobacteria are a diversified phylum of nitrogen-fixing, photo-oxygenic bacteria able to colonize a wide array of environments. In addition to their fundamental role as diazotrophs, they produce a plethora of bioactive molecules, often as secondary metabolites, exhibiting various biological and ecological functions to be further investigated. Among all the identified species, cyanobacteria are capable to embrace symbiotic relationships in marine environments with organisms such as protozoans, macroalgae, seagrasses, and sponges, up to ascidians and other invertebrates. These symbioses have been demonstrated to dramatically change the cyanobacteria physiology, inducing the production of usually unexpressed bioactive molecules. Indeed, metabolic changes in cyanobacteria engaged in a symbiotic relationship are triggered by an exchange of infochemicals and activate silenced pathways. Drug discovery studies demonstrated that those molecules have interesting biotechnological perspectives. In this review, we explore the cyanobacterial symbioses in marine environments, considering them not only as diazotrophs but taking into consideration exchanges of infochemicals as well and emphasizing both the chemical ecology of relationship and the candidate biotechnological value for pharmaceutical and nutraceutical applications.

Wax Ester Composition of Songbird Preen Oil Varies Seasonally and Differs between Sexes, Ages, and Populations.

Chemical signaling has been well studied in invertebrates and mammals but less so in birds, due to the longstanding misconception that olfaction is unimportant or even non-existent in this taxon. However, recent findings suggest that olfaction plays an important role in avian mate choice and reproductive behavior, similar to other taxa. The leading candidate source for compounds involved in avian chemical communication is preen oil, a complex mixture secreted from the uropygial gland. Preen oil contains volatile compounds and their potential wax ester precursors, and may act as a reproductive chemosignal. Reproductive signals are generally sexually dimorphic, age-specific, seasonally variable, and may also vary geographically. We tested whether preen oil meets these expectations by using gas chromatography to examine the wax ester composition of preen oil in song sparrows (Melospiza melodia). We found that the wax ester composition of preen oil was significantly different between sexes, age classes, seasons, and populations. Collectively, our results suggest that song sparrow preen oil meets the criteria of a chemical cue that may influence mate choice and reproduction. Our findings in song sparrows, which are sexually monomorphic in plumage, also parallel patterns described for dark-eyed juncos (Junco hyemalis), a closely related songbird with sexually dimorphic plumage. Behavioral tests are needed to confirm that song sparrows attend to the cues present in preen oil, but our findings support the increasingly accepted idea that chemical communication is common and widespread in birds as it is in other taxa.

Intraspecific chemical communication in microalgae.

Contents 516 I. 516 II. 518 III. 518 IV. 521 V. 523 VI. 523 VII. 526 526 References 526 SUMMARY: The relevance of infochemicals in the relationships between organisms is emerging as a fundamental aspect of aquatic ecology. Exchanges of chemical cues are likely to occur not only between organisms of different species, but also between conspecific individuals. Especially intriguing is the investigation of chemical communication in microalgae, because of the relevance of these organisms for global primary production and their key role in trophic webs. Intraspecific communication between algae has been investigated mostly in relation to sexuality and mating. The literature also contains information on other types of intraspecific chemical communication that have not always been explicitly tagged as ways to communicate to conspecifics. However, the proposed role of certain compounds as intraspecific infochemicals appears questionable. In this article, we make use of this plethora of information to describe the various instances of intraspecific chemical communication between conspecific microalgae and to identify the common traits and ecological significance of intraspecific communication. We also discuss the evolutionary implications of intraspecific chemical communication and the mechanisms by which it can be inherited. A special focus is the genetic diversity among conspecific algae, including the possibility that genetic diversity is an absolute requirement for intraspecific chemical communication.

Response of a Predatory ant to Volatiles Emitted by Aphid- and Caterpillar-Infested Cucumber and Potato Plants.

In response to herbivory by insects, various plants produce volatiles that attract enemies of the herbivores. Although ants are important components of natural and agro-ecosystems, the importance of herbivore-induced plant volatiles (HIPVs) as cues for ants for finding food sources have received little attention. We investigated responses of the ant Formica pratensis to volatiles emitted by uninfested and insect-infested cucumber (Cucumis sativus) and potato (Solanum tuberosum) plants. Cucumber plants were infested by the phloem-feeding aphid Aphis gossypii, the leaf chewer Mamestra brassicae or simultaneously by both insects. Potato plants were infested by either Aphis gossypii, by the leaf chewer Chrysodeixis chalcites or both. In olfactometer experiments, ants preferred volatile blends emitted by cucumber plants infested with M. brassicae caterpillars alone or combined with A. gossypii to volatiles of undamaged plants or plants damaged by A. gossypii only. No preference was recorded in choice tests between volatiles released by aphid-infested plants over undamaged plants. Volatiles emitted by potato plants infested by either C. chalcites or A. gossypii were preferred by ants over volatiles released by undamaged plants. Ants did not discriminate between potato plants infested with aphids and caterpillars over plants infested with aphids only. Plant headspace composition showed qualitative and/or quantitative differences between herbivore treatments. Multivariate analysis revealed clear separation between uninfested and infested plants and among herbivore treatments. The importance of HIPVs in indirect plant defence by ants is discussed in the context of the ecology of ant-plant interactions and possible roles of ants in pest management.

Low temperature and Daphnia-associated infochemicals promote colony formation of Scenedesmus obliquus and its harvesting.

OBJECTIVE: To explore the combined effects of temperature and Daphnia-associated infochemicals on colony formation of Scenedesmus obliquus to faciliate harvesting the algal biomass. RESULTS: A three-parameter modified Gaussian model fitted the changes of the number of cells per particle in S. obliquus induced by Daphnia culture filtrate well under any temperature. Decreases in temperature enhanced the induced-colony formation of Scenedesmus. The maximum colony size at 15-25 °C was significantly larger than those at 30-35 °C. An additional 1 or 2 days at low temperature was needed to reach the maximum colony size, which indicates the best harvest time for algal biomass. CONCLUSION: Induced-colony formation of Scenedesmus by Daphnia culture filtrate at 15-25 °C is recommended to settle algal cells. This condition facilitates harvesting the biomass.

Phenotypic plasticity in three Daphnia genotypes in response to predator kairomone: evidence for an involvement of chitin deacetylases.

The genetic background of inducible morphological defences in Daphnia is still largely unknown. Dissolved infochemicals from the aquatic larvae of the phantom midge Chaoborus induce so-called 'neck-teeth' in the first three post-embryonic stages of Daphnia pulex This defence has become a textbook example of inducible defences. In a target gene approach, by using three Daphnia genotypes which show a gradient of neck-teeth induction in response to equal amounts of kairomone, we report a high correlation of neck-teeth induction in Daphnia pulex and relative gene expression of two chitin deacetylases. Further, previous studies suggested genes from both the juvenoid and the insulin hormone signalling pathways as well as several morphogenetic genes downstream to be responsible for neck-teeth induction in D. pulex However, these data were not supported by our study. None of the three D. pulex clones showed an upregulation of these previously proposed candidate genes as a response to predator kairomone, which is interpreted as the result of refined methods used for both RNA sampling and kairomone enrichment yielding unambiguous results compared with earlier studies. The assessment of a clonal gradient of Daphnia in the presence and absence of infochemicals provides a promising approach to identify further genes involved in the induction of morphological defences by correlating gene expression and morphology.

The use of natural infochemicals for sustainable and efficient harvesting of the microalgae Scenedesmus spp. for biotechnology: insights from a meta-analysis.

Open raceway ponds are regarded as the most economically viable option for large-scale cultivation of microalgae for low to mid-value bio-products, such as biodiesel. However, improvements are required including reducing the costs associated with harvesting biomass. There is now a growing interest in exploiting natural ecological processes within biotechnology. We review how chemical cues produced by algal grazers induce colony formation in algal cells, which subsequently leads to their sedimentation. A statistical meta-analysis of more than 80 studies reveals that Daphnia grazers can induce high levels of colony formation and sedimentation in Scenedesmus obliquus and that these natural, infochemical induced sedimentation rates are comparable to using commercial chemical equivalents. These data suggest that natural ecological interactions can be co-opted in biotechnology as part of a promising, low energy and clean harvesting method for use in large raceway systems.

The smell of good food: volatile infochemicals as resource quality indicators.

Foraging success generally depends on various environmental and physiological factors. Particularly for organisms with limited motility such as gastropods, food searching is a very cost-intensive process. As energy gain through foraging is dependent on both resource quality and quantity, consumers have to be able to differentiate between varying resource items. The effectiveness of food searching could be increased through the perception of diet-derived chemical signals that convey information about a food resource's quality over a certain distance. This strategy would clearly help to optimize movement decisions. In this study, we investigated the foraging behaviour of a freshwater gastropod towards volatile signal substances released from benthic algae grown under high and low nutrient availability, representing high and low food quality, using behavioural assays in the laboratory. Our results demonstrate that volatile organic compounds (VOCs) serve as foraging kairomones for these aquatic, benthic herbivores. Further, we were able to show for the first time that snails are able to differentiate between high- and low-quality food sources, only by the perception of food odours alone (volatile infochemicals). Gas chromatography coupled with mass spectrometry demonstrated quantitative as well as qualitative differences in the chemical composition of the VOCs bouquet, dependent on algal nutrient content. Our results suggest that the recognition of resource quality via the reception of signal substances is likely to be adaptive for consumers with low mobility to maximize ingestion of high-quality resources.

Brindley's Glands Volatilome of the Predator Zelus renardii Interacting with Xylella Vectors.

Alien species must adapt to new biogeographical regions to acclimatise and survive. We consider a species to have become invasive if it establishes negative interactions after acclimatisation. Xylella fastidiosa Wells, Raju et al., 1986 (XF) represents Italy's and Europe's most recent biological invasion. In Apulia (southern Italy), the XF-encountered Philaenus spumarius L. 1758 (Spittlebugs, Hemiptera: Auchenorrhyncha) can acquire and transmit the bacterium to Olea europaea L., 1753. The management of XF invasion involves various transmission control means, including inundative biological control using Zelus renardii (ZR) Kolenati, 1856 (Hemiptera: Reduviidae). ZR is an alien stenophagous predator of Xylella vectors, recently entered from the Nearctic and acclimated in Europe. Zelus spp. can secrete semiochemicals during interactions with conspecifics and prey, including volatile organic compounds (VOCs) that elicit conspecific defence behavioural responses. Our study describes ZR Brindley's glands, present in males and females of ZR, which can produce semiochemicals, eliciting conspecific behavioural responses. We scrutinised ZR secretion alone or interacting with P. spumarius. The ZR volatilome includes 2-methyl-propanoic acid, 2-methyl-butanoic acid, and 3-methyl-1-butanol, which are consistent for Z. renardii alone. Olfactometric tests show that these three VOCs, individually tested, generate an avoidance (alarm) response in Z. renardii. 3-Methyl-1-butanol elicited the highest significant repellence, followed by 2-methyl-butanoic and 2-methyl-propanoic acids. The concentrations of the VOCs of ZR decrease during the interaction with P. spumarius. We discuss the potential effects of VOC secretions on the interaction of Z. renardii with P. spumarius.

Effects of chemical cues and prior experience on predator avoidance in crayfish.

Multisensory stimuli provide organisms with information to assess the threat present in the surroundings. Olfactory cues show dominance over other sensory modalities in the aquatic environment. The impact of chemical predator cues combined with experiences gained (learning) in species without previous contact is not fully understood. We investigated the foraging and shelter-seeking behaviour of naïve and experienced marbled crayfish Procambarus virginalis juveniles in response to the chemical signals of pumpkinseed Lepomis gibbosus alone and in combination with alarm chemicals produced by preyed-upon conspecifics. Naïve and experienced (previously exposed to pumpkinseed predation) juveniles were stocked in an arena with shelter and feed and exposed (1) to water from a tank containing a predator actively feeding on conspecifics, (2) water from a tank with predator only and (3) water only as control. Crayfish exposed to the combined stimuli avoided the inlet zone and gravitated to shelter zone of the arena to a greater extent than did those exposed to predator-only cues and the control. Regardless of the treatment, experienced crayfish showed significantly reduced interest in feeding. Our findings imply that crayfish response to threat-associated odours with the greatest potency when visual or tactile cues are present, while previous encounters with predators may make them more cautious.

Interspecific insights into direct and indirect effects of acetochlor on interactions between daphnids and microalgae: Toxic, trophic, and grazer-infochemical responses.

As the herbicide acetochlor (ACT) affects the plankton food web, this study investigated the effects of ACT and exocrine infochemicals from daphnids (after ACT exposure and/or starvation) on Scenedesmus obliquus growth, as well as the effects of ACT and starvation on life-history traits of Daphnia magna. Filtered secretions from daphnids increased algal ACT tolerance, dependent on different ACT exposure histories and food intake. Endogenous and secretory metabolite profiles of daphnids following ACT and/or starvation appear to be regulated by the fatty acid synthesis pathway and sulfotransferases and were related to energy allocation trade-offs. Oleic acid (OA) and octyl sulfate (OS), screened by secreted and somatic metabolomics, affected algal growth and ACT behavior in the algal culture in opposite ways. Trophic and non-trophic interspecific effects caused by ACT were observed in microalgae-daphnid microcosms, including algal growth inhibition, daphnid starvation, OA down-regulation, and OS up-regulation. Based on these findings, risk assessment of ACT on the freshwater plankton communities should take species interactions into account.

Volatile organic compounds in aquatic ecosystems - Detection, origin, significance and applications.

Volatile organic compounds (VOCs) include a broad range of compounds. Their production influences a large number of processes, having direct and secondary effects on different fields, such as climate change, economy and ecology. Although our planet is primarily covered with water (~70% of the globe surface), the information on aquatic VOCs, compared to the data available for the terrestrial environments, is still limited. Regardless of the difficulty in collecting and analysing data, because of their extreme complexity, diversification and important spatial-temporal emission variation, it was demonstrated that aquatic organisms are able to produce a variety of bioactive compounds. This production happens in response to abiotic and biotic stresses, evidencing the fundamental role of these metabolites, both in terms of composition and amount, in providing important ecological information and possible non-invasive tools to monitor different biological systems. The study of these compounds is an important and productive task with possible and interesting impacts in future practical applications in different fields. This review aims to summarize the knowledge on the aquatic VOCs, the recent advances in understanding their diverse roles and ecological impacts, the generally used methodology for their sampling and analysis, and their enormous potential as non-invasive, non-destructive and financeable affordable real-time biomonitoring tool, both in natural habitats and in controlled industrial situations. Finally, the possible future technical applications, highlighting their economic and social potential, such as the possibility to use VOCs as valuable alternative source of chemicals and as biocontrol and bioregulation agents, are emphasized.

Algal volatiles - the overlooked chemical language of aquatic primary producers.

Volatiles are important 'infochemicals' that play a crucial role in structuring life on our planet, fulfilling diverse functions in natural and artificial systems. Algae contribute significant quantities to the global budget of volatiles, but the ecological roles of aquatic volatiles are not well understood. In this review, we discuss the current knowledge of volatile compounds from freshwater and marine microalgae and marine macroalgae, with a focus on their ecological roles. We highlight the multiple reported functions of biogenic volatiles, ranging from intraspecific communication for reproduction, intra-bloom signalling and antioxidant functions, to various interspecific signal exchanges that may allow herbivores to locate them and function in defence against competitors and predators. Beyond reviewing our current understanding, we specifically highlight major knowledge gaps and emerging questions for algal volatile research. These novel perspectives have the potential to improve our understanding of aquatic ecosystems and thus need to be addressed in future research. Filling these gaps and addressing these questions will facilitate humanity's efforts to exploit aquatic volatiles in various applications.

Olfactory camouflage and communication in birds.

Smell is a sensory modality that is rarely considered in birds, but evidence is mounting that olfaction is an important aspect of avian behaviour and ecology. The uropygial gland produces an odoriferous secretion (preen oil) that can differ seasonally and between the sexes. These differences are hypothesized to function in olfactory camouflage, i.e. minimizing detection by nest predators (olfactory crypsis hypothesis), and/or intraspecific olfactory communication, particularly during breeding (sex semiochemical hypothesis). However, evidence for seasonal and sex differences in preen oil is mixed, with some studies finding differences and others not, and direct evidence for the putative function(s) of seasonal variation and sex differences in preen oil remains limited. We conducted a systematic review of the evidence for such changes in preen oil chemical composition, finding seasonal differences in 95% of species (57/60 species in 35 studies) and sex differences in 47% of species (28/59 species in 46 studies). We then conducted phylogenetic comparative analyses using data from 59 bird species to evaluate evidence for both the olfactory crypsis and sex semiochemical hypotheses. Seasonal differences were more likely in the incubating than non-incubating sex in ground-nesting species, but were equally likely regardless of incubation strategy in non-ground-nesting species. This result supports the olfactory crypsis hypothesis, if ground nesters are more vulnerable to olfactorily searching predators than non-ground nesters. Sex differences were more likely in species with uniparental than biparental incubation and during breeding than non-breeding, consistent with both the olfactory crypsis and sex semiochemical hypotheses. At present, the data do not allow us to disentangle these two hypotheses, but we provide recommendations that will enable researchers to do so.