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.

Marine Porifera host diverse microbial communities, which influence host metabolism and fitness. However, functional relationships between sponge microbiomes and metabolic signatures are poorly understood. We integrate microbiome characterization, metabolomics and microbial predicted functions of four coexisting Mediterranean sponges –Petrosia ficiformis,Chondrosia reniformis,Crambe crambeandChondrilla nucula. Microscopy observations reveal anatomical differences in microbial densities. Microbiomes exhibit strong species-specific trends.C. crambeshares many rare amplicon sequence variants (ASV) with the surrounding seawater. This suggests important inputs of microbial diversity acquired by selective horizontal acquisition. Phylum Cyanobacteria is mainly represented inC. nuculaandC. crambe. According to putative functions, the microbiome ofP. ficiformisandC. reniformisare functionally heterotrophic, whileC. crambeandC. nuculaare autotrophic. The four species display distinct metabolic profiles at single compound level. However, at molecular class level they share a “core metabolome”. Concurrently, we find global microbiome-metabolome association when considering all four sponge species. Within each species still, sets of microbe/metabolites are identified driving multi-omics congruence. Our findings suggest that diverse microbial players and metabolic profiles may promote niche diversification, but also, analogous phenotypic patterns of “symbiont evolutionary convergence” in sponge assemblages where holobionts co-exist in the same area.

The continuous outbreak of drug-resistant bacterial and viral infections imposes the need to search for new drug candidates. Natural products from marine bacteria still inspire the design of pharmaceuticals. Indeed, marine bacteria have unique metabolic flexibility to inhabit each ecological niche, thus expanding their biosynthetic ability to assemble unprecedented molecules. The One-Strain-Many-Compounds approach and tandem mass spectrometry allowed the discovery of a Shewanella aquimarina strain as a source of novel imidazolium alkaloids via molecular networking. The alkaloid mixture was shown to exert bioactivities such as: (a) antibacterial activity against antibiotic-resistant Staphylococcus aureus clinical isolates at 100 µg/mL, (b) synergistic effects with tigecycline and linezolid, (c) restoration of MRSA sensitivity to fosfomycin, and (d) interference with the biofilm formation of S. aureus 6538 and MRSA. Moreover, the mixture showed antiviral activity against viruses with and without envelopes. Indeed, it inhibited the entry of coronavirus HcoV-229E and herpes simplex viruses into human cells and inactivated poliovirus PV-1 in post-infection assay at 200 µg/mL. Finally, at the same concentration, the fraction showed anthelminthic activity against Caenorhabditis elegans, causing 99% mortality after 48 h. The broad-spectrum activities of these compounds are partially due to their biosurfactant behavior and make them promising candidates for breaking down drug-resistant infectious diseases.

Ocean acidification (OA) is a dramatic perturbation of seawater environments due to increasing anthropogenic emissions of CO₂. Several studies indicated that OA frequently induces marine biota stress and a reduction of biodiversity. Here, we adopted the macroalga Ulva prolifera as a model and applied a complementary multi-omics approach to investigate the metabolic profiles under normal and acidified conditions. Our results show that U. prolifera grows at higher rates in acidified environments. Consistently, we observed lower sucrose and phosphocreatine concentrations in response to a higher demand of energy for growth and a higher availability of essential amino acids, likely related to increased protein biosynthesis. In addition, pathways leading to signaling and deterrent compounds appeared perturbed. Finally, a remarkable shift was observed here for the first time in the fatty acid composition of triglycerides, with a decrease in the relative abundance of PUFAs towards an appreciable increase of palmitic acid, thus suggesting a remodeling in lipid biosynthesis. Overall, our studies revealed modulation of several biosynthetic pathways under OA conditions in which, besides the possible effects on the marine ecosystem, the metabolic changes of the alga should be taken into account considering its potential nutraceutical applications.

The Gram-negative Pantoea eucrina D2 was isolated from the marine sponge Chondrosia reniformis. Sponges were collected in a shallow volcanic vents system in Ischia island (South Italy), influenced by CO₂ emissions and lowered pH. The chemical diversity of the secondary metabolites produced by this strain, under different culture conditions, was explored by a combined approach including molecular networking, pure compound isolation and NMR spectroscopy. The metabolome of Pantoea cf. eucrina D2 yielded a very complex molecular network, allowing the annotation of several metabolites, among them two biosurfactant clusters: lipoamino acids and surfactins. The production of each class of metabolites was highly dependent on the culture conditions, in particular, the production of unusual surfactins derivatives was reported for the first time from this genus; interestingly the production of these metabolites only arises by utilizing inorganic nitrogen as a sole nitrogen source. Major components of the extract obtained under standard medium culture conditions were isolated and identified as N-lipoamino acids by a combination of 1D and 2D NMR spectroscopy and HRESI-MS analysis. Assessment of the antimicrobial activity of the pure compounds towards some human pathogens, indicated a moderate activity of leucine containing N-lipoamino acids towards Staphylococcus aureus, Staphylococcus epidermidis and a clinical isolate of the emerging food pathogen Listeria monocytogenes.

Ocean acidification (O.A.) influences the ecology of oceans and it may impact plant-animal interactions at various levels. Seagrass meadows located at acidified vents in the Bay of Naples (Italy) are considered an open window to forecast the effects of global-changes on aquatic communities. Epiphytic diatoms of the genus Cocconeis are abundant in seagrass meadows, including acidified environments, where they play key ecological roles. A still-unknown apoptogenic compound produced by Cocconeis triggers the suicide of the androgenic gland of Hippolyte inermis Leach 1816, a protandric hermaphroditic shrimp distributed in P. oceanica meadows located both at normal pH and in acidified vents. Feeding on Cocconeis sp. was proven important for the stability of the shrimp’s natural populations. Since O.A. affects the physiology of diatoms, we investigated if, in future scenarios of O.A., Cocconeis scutellum parva will still produce an effect on shrimp’s physiology. Cell densities of Cocconeis scutellum parva cultivated in custom-designed photobioreactors at two pH conditions (pH 7.7 and 8.2) were compared. In addition, we determined the effects of the ingestion of diatoms on the process of sex reversal of H. inermis and we calculated the % female on the total of mature individuals^-1 (F/mat). We observed significant differences in cell densities of C. scutellum parva at the two pH conditions_. In fact, the highest cell densities (148,808 ±13,935 cells. mm^-2) was obtained at day 13 (pH 7.7) and it is higher than the highest cell densities (38,066 (±4,166) cells. mm^-2, day 13) produced at pH 8.2. Diatoms cultured at acidified conditions changed their metabolism. In fact, diatoms grown in acidified conditions produced in H. inermis a proportion of females (F/mat 36.3 ±5.9%) significantly lower than diatoms produced at normal pH (68.5 ±2.8), and it was not significantly different from that elicited by negative controls (31.7 ±5.6%).