The natural product biosynthetic potential of Red Sea nudibranch microbiomes

Abstract

Background Antibiotic resistance is a growing problem that can be ameliorated by the discovery of novel drug candidates. Bacterial associates are often the source of pharmaceutically active natural products isolated from marine invertebrates, and thus, important targets for drug discovery. While the microbiomes of many marine organisms have been extensively studied, microbial communities from chemically-rich nudibranchs, marine invertebrates that often possess chemical defences, are relatively unknown. Methods We applied both culture-dependent and independent approaches to better understand the biochemical potential of microbial communities associated with nudibranchs. Gram-positive microorganisms isolated from nudibranchs collected in the Red Sea were screened for antibacterial and antitumor activity. To assess their biochemical potential, the isolates were screened for the presence of natural product biosynthetic gene clusters, including polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, using PCR. The microbiomes of the nudibranchs were investigated by high-throughput sequencing of 16S rRNA amplicons. Results In screens against five model microorganisms, 51% of extracts displayed antimicrobial activity against more than one organism, and 19% exhibited antitumor activity against Ehrlich’s ascites carcinoma. Sixty-four percent of isolates contained PKS and NRPS genes, suggesting their genomes contain gene clusters for natural product biosynthesis. Thirty-five percent were positive for more than one class of biosynthetic gene. These strains were identified as belonging to the Firmicutes and Actinobacteria phyla via 16S rRNA gene sequencing. In addition, 16S rRNA community amplicon sequencing revealed all bacterial isolates were present in the uncultured host-associated microbiome, although they were a very small percentage of the total community. Taken together, these results indicate that bacteria associated with marine nudibranchs are potentially a rich source of bioactive compounds and natural product biosynthetic genes.

Metabolomic Profiling and Molecular Networking of Nudibranch-Associated Streptomyces sp. SCSIO 001680

“…The detection of many compounds with cytotoxic activity and antimicrobial activity suggests that Streptomyces strain 63 could contribute to the defense of C. quadricolor from fungi, bacterial infections, and predation. In our previous study of strain 63, the ethyl acetate extract of the liquid culture medium exhibited antimicrobial and antitumor activity, and genomic DNA was shown to harbor several biosynthetic gene clusters, including polyketide synthase (PKS; type I and type II) and non-ribosomal peptide synthetase (NRPS) gene clusters [ 58 ]. Our results reinforce the hypothesis that the nudibranch-associated microbiome is a significant source of bioactive compounds, which may support the nudibranch’s chemical defense.…”

“…SCSIO 001680 was preserved as a lyophilized sample. It was cultivated as previously described [ 58 ]. Briefly, strain 63 was inoculated on an isolation medium R2A plate and incubated at 30 °C for five days.…”

Diversity and antimicrobial activity of marine nudibranch associated bacteria against tropical human skin pathogens

“…Therefore, the detection of polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes in the association of nudibranchs with bacteria could further explain their essential role in chemical defense in the nudibranchs. The purification of these nudibranch-associated bacterial genes has been conducted (Riyanti et al, 2009;Böhringer et al, 2017;Kristiana et al, 2020;Abdelrahman et al, 2021). The most recent study by Abdelrahman et al (2021) reported that nudibranch-associated bacteria have antibacterial activity and possess natural product gene clusters.…”

“…The purification of these nudibranch-associated bacterial genes has been conducted (Riyanti et al, 2009;Böhringer et al, 2017;Kristiana et al, 2020;Abdelrahman et al, 2021). The most recent study by Abdelrahman et al (2021) reported that nudibranch-associated bacteria have antibacterial activity and possess natural product gene clusters. In the present study, nudibranch-associated bacteria with potential bioactivity found in the Jepara coastal waters of the Java Sea were molecularly identified to determine their diversity, antimicrobial activity, and the presence of PKS and NRPS gene fragments.…”

Detection of Nudibranch Chromodoris quadricolor associated microbiome using two DNA extraction methods

“…The quality of the extraction methods to access diversity in the microbiome associated with C. quadricolor was examined by 16S rRNA community analysis and nextgeneration sequencing, whereas bioinformatics analyses and ecological statistics were performed as described previously [16]. The V4 region of 16S rRNA was amplified to prepare Illumina MiSeq libraries using environmental DNA protocol generated by Kozich et al [17].…”