Biology subjects

Concepcion, G. P.

Publications and source records attributed to Concepcion, G. P..

4 recordsLinked to original sources

bioRxiv2022

A conserved biosynthetic gene cluster is regulated by quorum sensing in a shipworm symbiont

Bacterial symbionts often provide critical functions for their hosts. For example, wood-boring bivalves called shipworms rely on cellulolytic endosymbionts for wood digestion. However, how the relationship between shipworms and their bacterial symbionts is formed and maintained remains unknown. Quorum sensing (QS) often plays an important role in regulating symbiotic relationships. We identified and characterized a QS system found in Teredinibacter sp. strain 2052S, a gill isolate of the wood-boring shipworm Bactronophorus cf. thoracites. We determined that 2052S produces the signal N-decanoyl-L-homoserine lactone (C10-HSL), and that this signal controls activation of a biosynthetic gene cluster co-located in the symbiont genome that is conserved among all symbiotic Teredinibacter isolates. We subsequently identified extracellular metabolites associated with the QS regulon, including ones linked to the conserved biosynthetic gene cluster, using mass spectrometry-based molecular networking. Our results demonstrate that QS plays an important role in regulating secondary metabolism in this shipworm symbiont. This information provides a step towards deciphering the molecular details of the relationship between these symbionts and their hosts. Furthermore, because shipworm symbionts harbor vast yet underexplored biosynthetic potential, understanding how their secondary metabolism is regulated may aid future drug discovery efforts using these organisms. IMPORTANCEBacteria play important roles as symbionts in animals ranging from invertebrates to humans. Despite this recognized importance, much is still unknown about the molecular details of how these relationships are formed and maintained. One of the proposed roles of shipworm symbionts is the production of bioactive secondary metabolites due to the immense biosynthetic potential found in shipworm symbiont genomes. Here, we report that a shipworm symbiont uses quorum sensing to coordinate activation of its extracellular secondary metabolism, including the transcriptional activation of a biosynthetic gene cluster that is conserved among many shipworm symbionts. This work is a first step towards linking quorum sensing, secondary metabolism, and symbiosis in wood-boring shipworms.

microbiology↗

bioRxiv2021

Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms, but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential. One Sentence SummarySomatostatin drug design by fish-hunting cone snails

biochemistry↗

bioRxiv2020

Inhibition of Biofilm Formation by Modified Oxylipins from the Shipworm Symbiont Teredinibacter turnerae

Bioactivity-guided purification of the culture broth of the shipworm endosymbiont Teredinibacter turnerae 991H.S.0a.06 yielded a new fatty acid, turneroic acid (1), and two previously described oxylipins (2-3). Turneroic acid (1) is an 18-carbon fatty acid decorated by a hydroxy group and an epoxide ring. Compounds 1-3 inhibited bacterial biofilm formation in Staphylococcus epidermidis, while only 3 showed antimicrobial activity against planktonic S. epidermidis. Comparison of the bioactivity of 1-3 with structurally related compounds indicated the importance of the epoxide moiety for selective and potent biofilm inhibition. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/393314v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@145f68org.highwire.dtl.DTLVardef@183df5borg.highwire.dtl.DTLVardef@bcdb6corg.highwire.dtl.DTLVardef@e9b9e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2019

Secondary metabolic symbiosis in shipworms (Teredinidae)

Shipworms play critical roles in recycling wood in the sea. Symbiotic bacteria supply enzymes that the organisms need for nutrition and wood degradation. Some of these bacteria have been grown in pure culture and have the capacity to make many secondary metabolites. However, little is known about whether such secondary metabolite pathways are represented in the symbiont communities within their hosts. In addition, little has been reported about the patterns of host-symbiont co-occurrence. Here, we collected shipworms from the United States, the Philippines, and Brazil, and cultivated symbiotic bacteria from their gills. We analyzed sequences from 22 shipworm gill metagenomes from seven shipworm species and from 23 cultivated symbiont isolates. Using (meta)genome sequencing, we demonstrate that the cultivated isolates represent all the major bacterial symbiont species and strains in shipworm gills. We show that the bacterial symbionts are distributed among shipworm hosts in consistent, predictable patterns. The symbiotic bacteria encode many biosynthetic gene cluster families (GCFs) for bioactive secondary metabolites, only <5% of which match previously described biosynthetic pathways. Because we were able to cultivate the symbionts, and sequence their genomes, we can definitively enumerate the biosynthetic pathways in these symbiont communities, showing that [~]150 out of [~]200 total biosynthetic gene clusters (BGCs) present in the animal gill metagenomes are represented in our culture collection. Shipworm symbionts occur in suites that differ predictably across a wide taxonomic and geographic range of host species, and collectively constitute an immense resource for the discovery of new biosynthetic pathways to bioactive secondary metabolites. ImportanceWe define a system in which the major symbionts that are important to host biology and to the production of secondary metabolites can be cultivated. We show that symbiotic bacteria that are critical to host nutrition and lifestyle also have an immense capacity to produce a multitude of diverse and likely novel bioactive secondary metabolites that could lead to the discovery of drugs, and that these pathways are found within shipworm gills. We propose that, by shaping associated microbial communities within the host, the compounds support the ability of shipworms to degrade wood in marine environments. Because these symbionts can be cultivated and genetically manipulated, they provide a powerful model for understanding how secondary metabolism impacts microbial symbiosis.

microbiology↗