Pyoverdines (PVDs) are a class of siderophores produced mostly by members of the genus Pseudomonas. Their primary function is to accumulate, mobilize, and transport iron necessary for cell metabolism. Moreover, PVDs also play a crucial role in microbes’ survival by mediating biofilm formation and virulence. In this review, we reorganize the information produced in recent years regarding PVDs biosynthesis and pathogenic mechanisms, since PVDs are extremely valuable compounds. Additionally, we summarize the therapeutic applications deriving from the PVDs’ use and focus on their role as therapeutic target themselves. We assess the current biotechnological applications of different sectors and evaluate the state-of-the-art technology relating to the use of synthetic biology tools for pathway engineering. Finally, we review the most recent methods and techniques capable of identifying such molecules in complex matrices for drug-discovery purposes.

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.

Coral reef survival is crucial for the socio-ecological interest of many countries, particularly for the Republic of Maldives, whose reef integrity influences the country’s livelihoods and economy. These ecosystems are being severely impacted by multiple stressors, leading to declines in biodiversity. In the last few decades, researchers have focused on studying coral-associated microorganisms (CAMs) and their symbiotic role in coral health and resilience. Metabarcoding analysis has been widely utilized to study CAM diversity under various conditions but provides limited information on their functional roles. Therefore, cultivation of bacterial strains remains indispensable for validating ecological and biotechnological hypotheses. In this study, we investigated the microbial community associated with two abundant corals in Maldives, Porites lobata and Acropora gemmifera, and evaluated the antimicrobial, antioxidant, and UV-protectant properties of 10 promising isolated strains. The selected CAMs, Pseudoalteromonas piscicida 39, Streptomyces parvus 79, Microbacterium sp. 92 (a potential novel species), and Micromonospora arenicola 93, exhibited antibiotic activity against a panel of pathogenic strains (MIC from 0.01 to 500 µg/mL), antioxidant (comparable effect to that of Trolox and ascorbic acid), and UV-screen activities (protection of human keratinocytes at 200 µg/mL). Genomes revealed their dual potential in contributing to coral restoration and drug discovery strategies. These findings highlight the biotechnological relevance of CAMs, representing an important step toward the identification of novel and bioactive bacterial species beneficial for coral reef ecosystems and human health.

3006 Background: Effective immunization requires efficient antigen delivery to antigen presenting cells (APCs). Antigens attached to the human antibody B11, targeting mannose receptors on APCs, have been shown to be processed and presented efficiently, and generate robust immune responses when combined with toll-like receptor (TLR) agonists. The CDX-1307 vaccine is composed of B11 fused with hCGβ, a tumor antigen correlated with advanced stage of disease and poor prognosis in a number of common epithelial cancers, but reported at variable rates of expression. Methods: Two phase I studies investigate intradermal (id) vs. systemic (iv) administration of CDX-1307. Patients with advanced epithelial cancers known to frequently express hCGβ receive 4 biweekly vaccinations of CDX-1307, alone or in combination with immunostimulants including GM-CSF (GM), the TLR3 agonist Poly-ICLC, and the TLR7/8 agonist resiquimod. Results: Dose-escalation is complete. In the id study, 37 patients received CDX-1307 at doses of 0.3, 1.0, and 2.5 mg, then 2.5 mg + GM, 2.5 mg + GM + Poly-ICLC, and 2.5 mg + GM + resiquimod. 2.5 mg + GM + Poly-ICLC + resiquimod is planned. In the iv study, 24 patients were treated at 1, 3, 10, and 30 mg, as well as 10 mg + GM and 30 mg + GM. 30 mg + GM + Poly-ICLC is enrolling. Treatment-related toxicities were generally mild to moderate with no dose-limiting toxicities, most frequently injection site reactions and fatigue in the id study, and fatigue, myalgia, and flu-like illness in the iv study. Humoral responses to hCGβ were increased in 56% of the analyzed patients receiving adjuvants. Serum hCGβ was frequently elevated at study entry or during treatment (males = 88%, females = 53%, pancreatic = 89%, colorectal = 78%, breast = 47%). hCGβ decreases were seen in some patients with immune responses. To date, a significant mixed response was seen in one patient with pancreatic cancer (id), while stable disease has been seen in 4 patients (2 with breast cancer = 25, 27 weeks and 2 with colorectal cancer = 9+ weeks). Conclusions: CDX-1307 is well tolerated and results in immune responses that are enhanced by immunostimulants. Elevated hCGβ was detected at a higher than expected frequency in these tumors.

T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues, thus representing a promising target for antibody-mediated therapy. To this end, we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma), and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody–drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1–expressing cell lines, but not on TIM-1–negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant antitumor activity in a clinically relevant dose range. Safety evaluation in nonhuman primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1–expressing tumors. Mol Cancer Ther; 15(12); 2946–54. ©2016 AACR.

Potentially toxic elements (PTEs) are persistent contaminants of terrestrial and aquatic ecosystems and heavy metals and metalloids represent a major environmental and health concern. Microbial bioremediation exploits the ability of bacteria, fungi, and microbial communities to modulate PTE fate through processes including biosorption, bioaccumulation, redox transformation, biomineralization, precipitation, chelation, and extracellular sequestration. This review examines the major advances of the last decade in the application of genomics, transcriptomics, proteomics, and metabolomics and their integration, to investigate molecular mechanisms of microbial adaptation to PTE contamination, supporting the selection of suitable microorganisms or microbial communities and the development of more effective bioremediation strategies. Genomic and metagenomic analyses enable the identification of genes and gene families associated with PTE resistance and adaptation, revealing both metal-specific and more general responses according to the presence of operons and/or cluster genes. Transcriptomic and proteomic approaches are applied to validate genetic potentialities, identifying mechanisms and protein mediators for transport, detoxification, redox homeostasis, and metal interactions. Metabolomics complements these approaches by characterizing metabolites involved in microbial responses, including organic acids, siderophores, biosurfactants, and extracellular polymeric substance-associated compounds. The review also discusses the advantages, limitations, and complementarity of the different omics approaches, emphasizing their impact in feasibility to move from ex situ to in situ applications. Finally, the review also addresses how omics layers could be combined across the phases of a real bioremediation project (screening, implementation, monitoring), highlighting integrated multi-omics approaches as powerful tools for developing and optimizing effective bioremediation strategies. Graphical abstract