Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC₅₀ values ≤ 25 μg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC₅₀ values < 5 μg/mL and LC₅₀/EC₅₀ ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities.

As significant drivers of cyanobacteria mortality, cyanophages have been known to regulate the population dynamics, metabolic activities, and community structure of this most important marine autotrophic picoplankton and, therefore, influence the global primary production and biogeochemical cycle in aquatic ecosystems. In the present study, a lytic Synechococcus phage, namely S-SZBM1, was isolated and identified. Cyanophage S-SZBM1 has a double-stranded DNA genome of 177,834 bp with a G+C content of 43.31% and contains a total of 218 predicted ORFs and six tRNA genes. Phylogenetic analysis and nucleotide-based intergenomic similarity suggested that cyanophage S-SZBM1 belongs to a new genus under the family Kyanoviridae. A variety of auxiliary metabolic genes (AMGs) that have been proved or speculated to relate to photosynthesis, carbon metabolism, nucleotide synthesis and metabolism, cell protection, and other cell metabolism were identified in cyanophage S-SZBM1 genome and may affect host processes during infection. In addition, 24 of 32 predicted structural proteins were identified by a high-throughput proteome analysis which were potentially involved in the assembly processes of virion. The genomic and proteomic analysis features of cyanophage S-SZBM1 offer a valuable insight into the interactions between cyanophages and their hosts during infection.

Bacterial biofilm can cause nosocomial recurrent infections and implanted device secondary infections in patients and strongly promotes development of pathogenic drug resistance in clinical treatments. Butenolide is an effective anti-macrofouling compound derived from a marine Streptomyces sp., but its antibiofilm efficacy remains largely unexplored. In the present study, the antibiofilm activities of butenolide were examined using biofilms formed by both Gram-positive and Gram-negative pathogenic model species. Four Escherichia coli strains, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) were used as targets in antibiofilm assays that examined the effects of butenolide, including the following: (i) on bacterial growth; (ii) in inhibiting biofilm formation and eradicating mature biofilm; (iii) on biofilm structures. In addition, the synergistic effect between butenolide with tetracycline was also examined. Butenolide not only effectively inhibited the biofilm formation but also eradicated pre-formed biofilms of tested bacteria. Fractional inhibitory concentration index (FICI) indicated that butenolide was a potential tetracycline enhancer against E. coli, P. aeruginosa, and MRSA. These results indicated that butenolide may hold a great potential as an effective antibiofilm agent to control and prevent biofilm-associated infections in future clinical treatments.

Biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) are one of the contributing factors to recurrent nosocomial infection in humans. There is currently no specific treatment targeting on biofilms in clinical trials approved by FDA, and antibiotics remain the primary therapeutic strategy. In this study, two anthraquinone compounds isolated from a rare actinobacterial strain Kitasatospora albolonga R62, 3,8-dihydroxy-l-methylanthraquinon-2-carboxylic acid (1) and 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid (2), together with their 10 commercial analogs 3–12 were evaluated for antibacterial and antibiofilm activities against MRSA, which led to the discovery of two potential antibiofilm anthraquinone compounds anthraquinone-2-carboxlic acid (6) and rhein (12). The structure-activity relationship analysis of these anthraquinones indicated that the hydroxyl group at the C-2 position of the anthraquinone skeleton played an important role in inhibiting biofilm formation at high concentrations, while the carboxyl group at the same C-2 position had a great influence on the antibacterial activity and biofilm eradication activity. The results of crystal violet and methyl thiazolyl tetrazolium staining assays, as well as scanning electron microscope and confocal scanning laser microscopy imaging of compounds 6 and 12 treatment groups showed that both compounds could disrupt preformed MRSA biofilms possibly by killing or dispersing biofilm cells. RNA-Seq was subsequently used for the preliminary elucidation of the mechanism of biofilm eradication, and the results showed upregulation of phosphate transport-related genes in the overlapping differentially expressed genes of both compound treatment groups. Herein, we propose that anthraquinone compounds 6 and 12 could be considered promising candidates for the development of antibiofilm agents.

In deep-sea hydrothermal vent environments, sulfur-oxidizing bacteria belonging to the clade SUP05 are crucial symbionts of invertebrate animals. Marine viruses, as the most abundant biological entities in the ocean, play essential roles in regulating the sulfur metabolism of the SUP05 bacteria. To date, vent-sponge-associated SUP05 and their phages have not been well documented. The current study analyzed the microbiome of Haplosclerida spp. sponges from hydrothermal vents in the Okinawa Trough and recovered the dominant SUP05 genome, designated VS-SUP05. Phylogenetic analysis showed that VS-SUP05 was closely related to endosymbiotic SUP05 strains from mussels living in deep-sea hydrothermal vent fields. Homology and metabolic pathway comparisons against free-living and symbiotic SUP05 revealed that the VS-SUP05 genome shared many features with the deep-sea mussel symbionts. Supporting a potentially-symbiotic lifestyle, the VS-SUP05 genome contained genes involved in the synthesis of essential amino acids and cofactors that are desired by the host. Analysis of sponge-associated viral sequences revealed putative VS-SUP05 phages, all of which were double-stranded viruses belonging to the families Myoviridae, Siphoviridae, Podoviridae, and Microviridae. Among the phage sequences, one contig contained metabolic genes (iscR, iscS, and iscU) involved in iron-sulfur cluster formation. Interestingly, genome sequence comparison revealed horizontal transfer of the iscS gene among phages, VS-SUP05 and other symbiotic SUP05, indicating an interaction between marine phages and SUP05 symbionts. Overall, our findings confirm the presence of SUP05 bacteria and their phages in sponges from deep-sea vents, and imply a beneficial interaction that allows adaptation of the host sponge to the hydrothermal vent environment. Importance Chemosynthetic SUP05 bacteria dominate the microbial communities of deep-sea hydrothermal vents around the world,. SUP05 bacteria utilize the reduced chemical compounds in vent fluids and commonly form symbioses with invertebrate organisms. This symbiotic relationship could be key to adapting to such unique and extreme environments. Viruses are the most abundant biological entities on the planet and have been identified in hydrothermal vent environments. However, their interactions with the symbiotic microbes of the SUP05 clade, along with their role in the symbiotic system, remain unclear. Here, using metagenomic sequence-based analyses, we determined that bacteriophages may support metabolism in SUP05 bacteria and play a role in the sponge-associated symbiosis system in hydrothermal vent environments.

The aim of this research is to explore the biological and chemical diversity of bacteria associated with a marine flatworm Paraplanocera sp., and to discover the bioactive metabolites from culturable strains. A total of 141 strains of bacteria including 45 strains of actinomycetes and 96 strains of other bacteria were isolated, identified and fermented on a small scale. Bioactive screening (antibacterial and cytotoxic activities) and chemical screening (ultra-performance liquid chromatography–mass spectrometry (UPLC-MS)) yielded several target bacterial strains. Among these strains, the ethyl acetate (EA) crude extract of Streptomyces sp. XY-FW47 fermentation broth showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus ATCC43300 (MRSA ATCC43300) and potent cytotoxic effects on HeLa cells. The UPLC-MS spectral analysis of the crude extract indicated that the strain XY-FW47 could produce a series of geldanamycins (GMs). One new geldanamycin (GM) analog, 4,5-dihydro-17-O-demethylgeldanamycin (1), and three known GMs (2–4) were obtained. All of these compounds were tested for antibacterial, cytotoxic, and antifungal activities, yet only GM (3) showed potent cytotoxic (HeLa cells, EC₅₀ = 1.12 μg/mL) and antifungal (Setosphaeria turcica MIC = 2.40 μg/mL) activities. Their structure–activity relationship (SAR) was also preliminarily discussed in this study.