Biology subjects

Haygood, M. G.

Publications and source records attributed to Haygood, M. G..

5 recordsLinked to original sources

bioRxiv2023

The dual role of TonB genes in turnerbactin uptake and carbohydrate utilization in the shipworm symbiont Teredinibacter turnerae

Teredinibacter turnerae is an intracellular bacterial symbiont that resides in the gills of shipworms, wood-eating bivalve mollusks. This bacterium produces a catechol siderophore, turnerbactin, required for the survival of this bacterium under iron limiting conditions. The turnerbactin biosynthetic genes are contained in one of the secondary metabolite clusters conserved among T. turnerae strains. However, Fe(III)-turnerbactin uptake mechanisms are largely unknown. Here, we show that the first gene of the cluster, fttA a homologue of Fe(III)-siderophore TonB-dependent outer membrane receptor (TBDR) genes is indispensable for iron uptake via the endogenous siderophore, turnerbactin, as well as by an exogenous siderophore, amphi-enterobactin, ubiquitously produced by marine vibrios. Furthermore, three TonB clusters containing four tonB genes were identified, and two of these genes, tonB1b and tonB2, functioned not only for iron transport but also for carbohydrate utilization when cellulose was a sole carbon source. Gene expression analysis revealed that none of the tonB genes and other genes in those clusters were clearly regulated by iron concentration while turnerbactin biosynthesis and uptake genes were up-regulated under iron limiting conditions, highlighting the importance of tonB genes even in iron rich conditions, possibly for utilization of carbohydrates derived from cellulose.

microbiology↗

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

Initial efficacy determination and resistance profile of anti-Acinetobacter antibiotics, turnercyclamycins

Drug-resistant Acinetobacter is a challenging, deadly pathogen of increasing prevalence in the US healthcare system. Recently, we described a series of lipopeptides, the turnercyclamycins, which retain potency against Acinetobacter strains that are resistant to the last-line antibiotic, colistin. To further evaluate the potential of turnercyclamycins, we completed mouse efficacy, pharmacokinetics, and toxicity studies. These demonstrate that turnercyclamycin A has a pharmacological profile with similarity to other lipopeptides that are in clinical use. Turnercyclamycin A was well tolerated in mice up to 25 mg/kg, and exhibited >99% and >98% reduction in bacterial load compared to vehicle control in a thigh infection model at 25 and 12.5 mg/kg, respectively. This result closely reflected the anticipated effectiveness based upon in vitro activity and was similar to the colistin control. Acinetobacter strains resistant to colistin often harbor the mcr-1 resistance gene. Here, we show that the effectiveness of turnercyclamycins against Escherichia coli is not greatly altered by mcr-1 (0- to 2-fold) whereas there is a 16-fold increase in the colistin minimal inhibitory concentration when mcr-1 is present. These data suggest that turnercyclamycins are suitable for further investigation and optimization as anti-Acinetobacter lead compounds.

pharmacology and toxicology↗

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↗