Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes. In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular, and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS), and polyketide synthases (PKS) genes were screened. Molecular analysis revealed that 95% of the planctomycetes potentially have one or both secondary bioactive genes; 85% amplified with PKS-I primers and 55% with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8, and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43%) and antibacterial (54%) activity against C. albicans and B. subtilis, respectively. Bioactivity was observed in strains from Rhodopirellula lusitana, R. rubra, R. baltica, Roseimaritima ulvae, and Planctomyces brasiliensis. This study confirms the bioactive capacity of Planctomycetes to produce antimicrobial compounds and encourages further studies envisaging molecule isolation and characterization for the possible discovery of new drugs.

The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms’ genomes, the development of more representative disease models and improvement of techniques, technologies, and computation applied to biology are advances that will foster drug discovery in upcoming years. In this paper, several aspects of current methodologies for drug discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm and antiquorum sensing, anticancer and neuroprotectors are considered. For drug discovery, two different complementary approaches can be applied: classical pharmacology, also known as phenotypic drug discovery, which is the historical basis of drug discovery, and reverse pharmacology, also designated target-based drug discovery. Screening methods based on phenotypic drug discovery have been used to discover new natural products mainly from terrestrial origin. Examples of the discovery of marine natural products are provided. A section on future trends provides a comprehensive overview on recent advances that will foster the pharmaceutical industry.

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There is a strong need to develop new drugs against many severe diseases. Therapy resistance is a major problem, for instance, in infectious diseases and cancer. Drug discovery has again turned to nature to search for molecules that can become drug leads. Although many bacterial phyla are extensively studied, some, like the Planctomycetes, remain largely unexplored as potential sources of new leads. Planctomycetes form a diverse group of bacteria with peculiar characteristics such as division by polar budding and absence of the FtsZ gene. Furthermore, they exhibit large genomes up to 12.5 Mb, and possess a high number of secondary metabolites as assessed by in silico genomic analysis. These characteristics have also revealed the presence of potential anticancer activity. Based on these promising characteristics, we wanted to investigate Planctomycetes as a source for natural products with anticancer properties. Organic and aqueous extracts were obtained from cultivated Planctomycetes strains originated from a variety of habitats such as marine systems (free living or attached to marine algae), deep marine iron hydroxide deposits, brackish water and glacier ice system. The extracts were screened for ability to inhibit cell growth, or induce cell death on two cancer cell lines, the human prostatic cancer cell line PC3, and human acute myeloid leukaemia (AML) cell line MOLM-13, as well as normal rat kidney epithelial cell line (NRK). Out of 39 strains, five exhibited cytotoxicity toward NRK cells, whereas 32 of the strains were toxic to the AML cell line, and four were toxic to the PC3 cell line. Two strains showed high toxicity and selectivity toward both the cancer cell lines over the NRK-cells, and are potential producers of anti-cancer compounds. We found no correlation between bioactivity and strains habitat and geographic location but regarding phylogeny some Rhodopirellula spp. showed higher toxicity toward MOLM-13 cells. These results from the first anticancer screening with Planctomycetes showed that these peculiar microorganisms should be further explored for anti-cancer compounds, and that more effort must be put in providing culture collections for drug development purposes.

The Water Framework Directive (WFD) is used to evaluate the water quality of aquatic ecosystems. Phytoplankton is the only biological element considered in the reservoirs water quality assessment. In this study, we aimed to assess the use of the bacterioplankton community as an indicator of water quality, using a culture-independent assay (denaturing gradient gel electrophoresis, DGGE). Four Portuguese reservoirs (Miranda, Pocinho, Aguieira and Alqueva) were analysed in four periods (autumn 2018, spring and autumn 2019, and spring 2020). Bacterial total abundance had similar values for Miranda, Pocinho and Aguieira, and generally lower values for Alqueva. Diversity and richness values did not show a clear trend. Negative correlations were observed between some nutrients and the bacterial community. Overall, members of Actinobacteria, Bacteroidetes, Cyanobacteria, Nitrospirae and Proteobacteria were identified in all sampling sites. In Alqueva, no spatial, temporal or water body quality relationships with bacterial community were observed, which may be due to its higher size, low water velocity rate and higher residence times. However, in Miranda, Pocinho and Aguieira, a strong spatial and temporal bacterial community dynamic was observed. Furthermore, the presence of some species (e.g., Acinetobacter sp.) may reflect the poor water quality that was not detected by the WFD approach.