Carmine Buonocore

The increasing incidence of jellyfish blooms and the consequent accumulation of jellyfish bycatch impose the need to explore new strategies for the valorization of this marine biomass. Jellyfish are attracting growing interest as sustainable sources of proteins, collagen, and bioactive peptides with potential applications in food, nutraceutical, and biotechnological fields. In this work, the Mediterranean jellyfish Cotylorhiza tuberculata was investigated as a source of proteinaceous fractions and enzymatic hydrolysates. Umbrella and oral arms were processed separately by phosphate-buffered saline (PBS) extraction, followed by sequential enzymatic digestion of the insoluble material with pepsin and collagenase. The resulting extracts were fractionated by membrane ultrafiltration and characterized for protein content. The fractions were then tested for antioxidant activity, angiotensin-I-converting enzyme (ACE) inhibition, effects on A2058 melanoma and HaCaT keratinocyte viability, and modulation of IL-6 response in intestinal Caco-2 cells. Collagenase-derived fractions showed the highest antioxidant activity, while ACE-inhibitory activity was mainly associated with pepsin-derived samples. Selected umbrella-derived fractions differentially affected A2058 and HaCaT cell viability. Finally, preliminary Caco-2 experiments indicated limited, fraction-dependent modulation of IL-6 levels. Overall, these results suggest that C. tuberculata may represent a useful source of protein-derived fractions with in vitro antioxidant and ACE-inhibitory activities, supporting further investigation of jellyfish bycatch as a resource for functional ingredients.

Rhamnolipids are a class of glycolipids known for their surface and emulsifying activity. These molecules, produced by a few Gram-negative genera, mostly Pseudomonas, offer natural alternatives to synthetic surfactants in different industrial fields. This study examines the emulsifying and encapsulation performance of Rhamnolipids derived from the marine Antarctic bacterium Pseudomonas gessardii M15, comparing its emulsification ability and stability with those of commercial surfactants, Sodium dodecyl sulfate (SDS) and sucrose esters (SE), under extreme conditions of temperature and pH. The Rhamolipids were used to encapsulate Coenzyme Q10 with Arabic gum as the carrier matrix. Rhamnolipids exhibited surface and emulsifying activity comparable to that of SDS and superior to SE at neutral and basic pH levels. Their performance declined under acidic conditions, whereas exposure to 90 °C had no significant effects. The encapsulation efficiency of Coenzyme Q10 was significantly higher in the case of Rhamnolipids, with a percentage of encapsulated compound of 99.6 ± 0.2%, compared to the 38.2 ± 7.1% found when SDS was used. Rhamnolipids extracted from Pseudomonas gessardii M15 exhibit strong potential as a natural surfactant, particularly in formulations that require thermal stability and effective encapsulation. These findings support its use as a sustainable alternative to synthetic agents in diverse industrial settings.

Over the past years, with the growing interest in sustainable biomaterials, marine collagen has been emerging as an interesting alternative to bovine collagen. It is more easily absorbed by the body and has higher bioavailability. In this study, collagen was extracted from Dicentrarchus labrax (sea bass) skin, a fishery by-product, thus valorizing waste streams while reducing environmental impact. To overcome the intrinsic weak mechanical of collagen, it was combined with chitosan to produce composite scaffolds for skin tissue engineering. The incorporation of collagen proved crucial for scaffold performance: (i) it promoted the formation of an open-pore architecture, favorable for cell infiltration and proliferation; (ii) it enhanced swelling behavior suitable for exudate absorption and maintenance of a moist wound environment; (iii) by tuning the chitosan/collagen ratio, it enabled us to control the degradation rate; (iv) it conferred antioxidant properties; and (iv) by adjusting collagen/chitosan concentrations, it allowed fine-tuning of mechanical properties, ensuring sufficient strength to resist stresses encountered during wound healing. In vitro assays demonstrated that the scaffolds were non-cytotoxic and effectively supported mouse adipose tissue fibroblasts’ adhesion and proliferation. Finally, all formulations exhibited marked bactericidal activity against the human pathogen Staphylococcus aureus and the methicillin-resistant Staphylococcus aureus, with a Log reduction greater than 3 (a reduction of at least 99.9% in bacterial growth) compared to the control. Collectively, these findings highlight collagen not only as a sustainable resource but also as a functional component that drives the structural, physicochemical, biological, and antimicrobial performance of chitosan/collagen scaffolds for skin tissue engineering.

Marine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in genomics, metabolomics, and bioinformatics. Furthermore, innovative isolation and cultivation approaches have improved the isolation of rare and difficult-to-culture marine microbes, leading to the identification of novel secondary metabolites. Advances in synthetic biology and metabolic engineering have further optimized natural product yields and the generation of novel compounds with improved bioactive properties. This review highlights key developments in the exploitation of marine bacteria, fungi, and microalgae for the discovery of novel natural products with potential applications in diverse fields, underscoring the immense potential of marine microorganisms in the growing Blue Economy sector.

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase.

Microbial biosurfactants have garnered significant interest from industry due to their lower toxicity, biodegradability, activity at lower concentrations and higher resistance compared to synthetic surfactants. The deep‐sea Rhodococcus sp. I2R has been identified as a producer of glycolipid biosurfactants, specifically succinoyl trehalolipids, which exhibit antiviral activity. However, genome mining of this bacterium has revealed a still unexplored repertoire of biosurfactants. The microbial genome was found to host five non‐ribosomal peptide synthetase (NRPS) gene clusters containing starter condensation domains that direct lipopeptide biosynthesis. Genomics and mass spectrometry (MS)‐based metabolomics enabled the linking of two NRPS gene clusters to the corresponding lipopeptide families, leading to the identification of 20 new cyclolipopeptides, designated as rhodoheptins, and 33 new glycolipopeptides, designated as rhodamides. An integrated in silico gene cluster and high‐resolution MS/MS data analysis allowed us to elucidate the planar structure, inference of stereochemistry and reconstruction of the biosynthesis of rhodoheptins and rhodamides. Rhodoheptins are cyclic heptapeptides where the N‐terminus is bonded to a β‐hydroxy fatty acid forming a macrolactone ring with the C‐terminal amino acid residue. Rhodamides are linear 14‐mer glycolipopeptides with a serine‐ and alanine‐rich peptide backbone, featuring a distinctive pattern of acetylation, glycosylation and succinylation. These molecules exhibited biosurfactant activity in the oil‐spreading assay and showed moderate antiproliferative effects against human A375 melanoma cells.

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.

Staphylococcus aureus is a Gram-positive opportunistic human pathogen responsible for severe infections and thousands of deaths annually, mostly due to its multidrug-resistant (MDR) variants. The cell membrane has emerged as a promising new therapeutic target, and lipophilic molecules, such as biosurfactants, are currently being utilized. Herein, we evaluated the antimicrobial activity of a rhamnolipids mixture produced by the Antarctic marine bacterium Pseudomonas gessardii M15. We demonstrated that our mixture has bactericidal activity in the range of 12.5–50 µg/mL against a panel of clinical MDR isolates of S. aureus, and that the mixture eradicated the bacterial population in 30 min at MIC value, and in 5 min after doubling the concentration. We also tested abilities of RLs to interfere with biofilm at different stages and determined that RLs can penetrate biofilm and kill the bacteria at sub-MICs values. The mixture was then used to functionalize a cotton swab to evaluate the prevention of S. aureus proliferation. We showed that by using 8 µg of rhamnolipids per swab, the entire bacterial load is eradicated, and just 0.5 µg is sufficient to reduce the growth by 99.99%. Our results strongly indicate the possibility of using this mixture as an additive for wound dressings for chronic wounds.

Although several antibiotics are already widely used against a large number of pathogens, the discovery of new antimicrobial compounds with new mechanisms of action is critical today in order to overcome the spreading of antimicrobial resistance among pathogen bacteria. In this regard, marine organisms represent a potential source of a wide diversity of unique secondary metabolites produced as an adaptation strategy to survive in competitive and hostile environments. Among the multidrug-resistant Gram-negative bacteria, Pseudomonas aeruginosa is undoubtedly one of the most important species due to its high intrinsic resistance to different classes of antibiotics on the market and its ability to cause serious therapeutic problems. In the present review, we first discuss the general mechanisms involved in the antibiotic resistance of P. aeruginosa. Subsequently, we list the marine molecules identified up until now showing activity against P. aeruginosa, dividing them according to whether they act as antimicrobial or anti-virulence compounds.