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Genetics play an important role in the development of metabolic diseases. However, the relative influence of genetic variation on metabolism is not well defined, particularly in tissues, where metabolic dysfunction that leads to disease occurs. We used inbred strains of laboratory mice to evaluate the impact of genetic variation on the metabolomes of tissues that play central roles in metabolic diseases. We chose a set of four common inbred strains that have different levels of susceptibility to obesity, insulin resistance, and other common metabolic disorders. At the ages used, and under standard husbandry conditions, these lines are not overtly diseased. Using global metabolomics profiling, we evaluated water-soluble metabolites in liver, skeletal muscle, and adipose from A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ mice fed a standard mouse chow diet. We included both males and females to assess the relative influence of strain, sex, and strain-by-sex interactions on metabolomes. The mice were also phenotyped for systems level traits related to metabolism and energy expenditure. Strain explained more variation in the metabolite profile than did sex or its interaction with strain across each of the tissues, especially in liver. Purine and pyrimidine metabolism and pathways related to amino acid metabolism were identified as pathways that discriminated strains across all three tissues. Based on the results from ANOVA, sex and sex-by-strain interaction had modest influence on metabolomes relative to strain, suggesting that the tissue metabolome remains largely stable across sexes consuming the same diet. Our data indicate that genetic variation exerts a fundamental influence on tissue metabolism.

Herbal remedies are increasing in popularity as treatments for metabolic conditions such as obesity and Type 2 Diabetes. One potential therapeutic option is fenugreek seeds ( Trigonella foenum-graecum ), which have been used for treating high cholesterol and Type 2 diabetes. A proposed mechanism for these benefits is through alterations in the microbiome, which impact mammalian host metabolic function. This study used untargeted metabolomics to investigate the fenugreek-induced alterations in the intestinal, liver, and serum profiles of mice fed either a 60% high-fat or low-fat control diet each with or without fenugreek supplementation (2% w / w ) for 14 weeks. Metagenomic analyses of intestinal contents found significant alterations in the relative composition of the gut microbiome resulting from fenugreek supplementation. Specifically, Verrucomicrobia, a phylum containing beneficial bacteria which are correlated with health benefits, increased in relative abundance with fenugreek. Metabolomics partial least squares discriminant analysis revealed substantial fenugreek-induced changes in the large intestines. However, it was observed that while the magnitude of changes was less, significant modifications were present in the liver tissues resulting from fenugreek supplementation. Further analyses revealed metabolic processes affected by fenugreek and showed broad ranging impacts in multiple pathways, including carnitine biosynthesis, cholesterol and bile acid metabolism, and arginine biosynthesis. These pathways may play important roles in the beneficial effects of fenugreek.

The environmental conditions experienced by microbial communities are rarely fully simulated in the laboratory. Researchers use experimental containers ("bottles"), where natural samples can be manipulated and evaluated. However, container-based methods are subject to "bottle effects": changes that occur when enclosing the plankton community that are often times unexplained by standard measures like pigment and nutrient concentrations. We noted variability in a short-term, nutrient amendment experiment during a 2019 Lake Erie, Microcystis spp. bloom. We observed changes in heterotrophic bacteria activity (transcription) on a time-frame consistent with a response to experimental changes in nutrient availability, demonstrating how the often overlooked microbiome of cyanobacterial blooms can be altered. Samples processed at the time of collection (T0) contained abundant transcripts from Bacteroidetes, which reduced in abundance during incubation in all bottles, including controls. Significant biological variability in the expression of Microcystis -infecting phage was observed between replicates, with phosphate-amended treatments showing a 10-fold variation. The expression patterns of Microcystis -infecting phage were significantly correlated with ∼35% of Microcystis -specific functional genes and ∼45% of the cellular-metabolites measured across the entire microbial community, suggesting phage activity not only influenced Microcystis dynamics, but the biochemistry of the microbiome. Our observations demonstrate how natural heterogeneity among replicates can be harnessed to provide further insight on virus and host ecology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pound, Martin, Zepernick, Christopher, Howard, Castro, Campagna, Boyer, Bullerjahn, Chaffin and Wilhelm.)

Muscle builders frequently consume protein supplements, but little is known about their effect on the gut microbiota. This study compared the gut microbiome and metabolome of self-identified muscle builders who did or did not report consuming a protein supplement. Twenty-two participants (14 males and 8 females) consumed a protein supplement (PS), and seventeen participants (12 males and 5 females) did not (No PS). Participants provided a fecal sample and completed a 24-h food recall (ASA24). The PS group consumed significantly more protein (118 ± 12 g No PS vs. 169 ± 18 g PS, p = 0.02). Fecal metabolome and microbiome were analyzed by using untargeted metabolomics and 16S rRNA gene sequencing, respectively. Metabolomic analysis identified distinct metabolic profiles driven by allantoin (VIP score = 2.85, PS 2.3-fold higher), a catabolic product of uric acid. High-protein diets contain large quantities of purines, which gut microbes degrade to uric acid and then allantoin. The bacteria order Lactobacillales was higher in the PS group (22.6 ± 49 No PS vs. 136.5 ± 38.1, PS (p = 0.007)), and this bacteria family facilitates purine absorption and uric acid decomposition. Bacterial genes associated with nucleotide metabolism pathways (p < 0.001) were more highly expressed in the No PS group. Both fecal metagenomic and metabolomic analyses revealed that the PS group’s higher protein intake impacted nitrogen metabolism, specifically altering nucleotide degradation.

Recent scientific evidence suggests that traits energy and fatigue are two unique unipolar moods with distinct mental and physical components. This exploratory study investigated the correlation between mental energy (ME), mental fatigue (MF), physical energy (PE), physical fatigue (PF), and the gut microbiome. The four moods were assessed by survey, and the gut microbiome and metabolome were determined from 16 S rRNA analysis and untargeted metabolomics analysis, respectively. Twenty subjects who were 31 ± 5 y, physically active, and not obese (26.4 ± 4.4 kg/m2) participated. Bacteroidetes (45%), the most prominent phyla, was only negatively correlated with PF. The second most predominant and butyrate-producing phyla, Firmicutes (43%), had members that correlated with each trait. However, the bacteria Anaerostipes was positively correlated with ME (0.048, p = 0.032) and negatively with MF (−0.532, p = 0.016) and PF (−0.448, p = 0.048), respectively. Diet influences the gut microbiota composition, and only one food group, processed meat, was correlated with the four moods—positively with MF (0.538, p = 0.014) and PF (0.513, p = 0.021) and negatively with ME (−0.790, p < 0.001) and PE (−0.478, p = 0.021). Only the Firmicutes genus Holdemania was correlated with processed meat (r = 0.488, p = 0.029). Distinct metabolic profiles were observed, yet these profiles were not significantly correlated with the traits. Study findings suggest that energy and fatigue are unique traits that could be defined by distinct bacterial communities not driven by diet. Larger studies are needed to confirm these exploratory findings.

Liquid chromatography-high-resolution mass spectrometry (LC-MS)-based metabolomics aims to identify and quantify all metabolites, but most LC-MS peaks remain unidentified. Here we present a global network optimization approach, NetID, to annotate untargeted LC-MS metabolomics data. The approach aims to generate, for all experimentally observed ion peaks, annotations that match the measured masses, retention times and (when available) tandem mass spectrometry fragmentation patterns. Peaks are connected based on mass differences reflecting adduction, fragmentation, isotopes, or feasible biochemical transformations. Global optimization generates a single network linking most observed ion peaks, enhances peak assignment accuracy, and produces chemically informative peak-peak relationships, including for peaks lacking tandem mass spectrometry spectra. Applying this approach to yeast and mouse data, we identified five previously unrecognized metabolites (thiamine derivatives and N-glucosyl-taurine). Isotope tracer studies indicate active flux through these metabolites. Thus, NetID applies existing metabolomic knowledge and global optimization to substantially improve annotation coverage and accuracy in untargeted metabolomics datasets, facilitating metabolite discovery., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Glucocorticoids (GCs) are widely used in medicine for their role in the treatment of autoimmune-mediated conditions, certain cancers, and organ transplantation. The transcriptional activities GCs elicit include transrepression, postulated to be responsible for the anti-inflammatory activity, and transactivation, proposed to underlie the undesirable side effects associated with long-term use. A GC analogue that could elicit only transrepression and beneficial transactivation properties would be of great medicinal value and is highly sought after. In this study, a series of 1-(4-substituted phenyl)pyrazole-based GC analogues were synthesized, biologically screened, and evaluated for SARs leading to the desired activity. Activity observed in compounds bearing an electron deficient arylpyrazole moiety showed promise toward a dissociated steroid, displaying transrepression while having limited transactivation activity. In addition, compounds 11aa and 11ab were found to have anti-inflammatory efficacy comparable to that of dexamethasone at 10 nM, with minimal transactivation activity and no reduction of insulin secretion in cultured rat 832/13 beta cells., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Induced ovulation of small pre-ovulatory follicles reduced pregnancy rates, embryo survival, day seven embryo quality, and successful embryo cleavage in beef cows undergoing fixed-time artificial insemination. RNA-sequencing of oocytes and associated cumulus cells collected from pre-ovulatory follicles 23 h after gonadotropin-releasing hormone (GnRH) administration to induce the pre-ovulatory gonadotropin surge suggested reduced capacity for glucose metabolism in cumulus cells of follicles ≤11.7 mm. We hypothesized that the follicular fluid metabolome influences metabolic capacity of the cumulus-oocyte complex and contributes to reduced embryo cleavage and quality grade observed following induced ovulation of small follicles. Therefore, we performed a study to determine the correlation between pre-ovulatory follicle diameter and follicular fluid metabolome profiles in lactating beef cows (Angus, n = 130). We synchronized the development of a pre-ovulatory follicle and collected the follicular contents approximately 20 h after GnRH administration. We then performed ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolomic studies on 43 follicular fluid samples and identified 38 metabolites within pre-ovulatory follicles of increasing size. We detected 18 metabolites with a significant, positive correlation to follicle diameter. Individual and pathway enrichment analysis of significantly correlated metabolites suggest that altered glucose and amino acid metabolism likely contribute to reduced developmental competence of oocytes when small pre-ovulatory follicles undergo induced ovulation.

Daptomycin is a cyclic lipopeptide antibiotic used in the clinic for treatment of severe enterococcal infections. Recent reports indicate that daptomycin targets active cellular processes, specifically, peptidoglycan biosynthesis. Within, we examined the efficacy of daptomycin against Enterococcus faecalis under a range of environmental growth conditions including inhibitors that target active cellular processes. Daptomycin was far less effective against cells in late stationary phase compared to cells in exponential phase, and this was independent of cellular ATP levels. Further, the addition of either the de novo protein synthesis inhibitor chloramphenicol or the fatty acid biosynthesis inhibitor cerulenin induced survival against daptomycin far better than controls. Alterations in metabolites associated with peptidoglycan synthesis correlated with protection against daptomycin. This was further supported as removal of peptidoglycan induced physiological daptomycin tolerance, a synergistic relation between daptomycin and fosfomycin, an inhibitor of the fist committed step peptidoglycan synthesis, was observed, as well as an additive effect when daptomycin was combined with ampicillin, which targets crosslinking of peptidoglycan strands. Removal of the peptidoglycan of Enterococcus faecium, Staphylococcus aureus, and Bacillus subtilis also resulted in significant protection against daptomycin in comparison to whole cells with intact cell walls. Based on these observations, we conclude that bacterial growth phase and metabolic activity, as well as the presence/absence of peptidoglycan are major contributors to the efficacy of daptomycin., Competing Interests: The authors have declared that no competing interests exist.

Dichloromethane (DCM) is an anthropogenic pollutant with ozone destruction potential that is also formed naturally. Under anoxic conditions, fermentation of DCM to acetate and formate has been reported in axenic culture Dehalobacterium formicoaceticum, and to acetate, H 2 and CO 2 in mixed culture RM, which harbors the DCM degrader 'Candidatus Dichloromethanomonas elyunquensis'. RM cultures produced 28.1 ± 2.3 μmol of acetate from 155.6 ± 9.3 μmol DCM, far less than the one third (i.e., about 51.9 µmol) predicted based on the assumed fermentation model, and observed in cultures of Dehalobacterium formicoaceticum. Temporal metabolite analyses using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy revealed that no 13 C-labeled acetate was formed in 13 C-DCM-grown RM cultures, indicating acetate was not a direct product of DCM metabolism. The data were reconciled with DCM mineralization and H 2 consumption via CO 2 reduction to acetate and methane by homoacetogenic and methanogenic partner populations, respectively. In contrast, Dehalobacterium formicoaceticum produced 13 C-labeled acetate and formate from 13 C-DCM, consistent with a fermentation pathway. Free energy change calculations predicted that organisms with the mineralization pathway are the dominant DCM consumers in environments with H 2 <100 ppmv. These findings have implications for carbon and electron flow in environments where DCM is introduced through natural production processes or anthropogenic activities.

Introduction: Beef is the most consumed red meat in the United States, and the US is the largest producer and consumer of beef cattle globally. Feed is one of the largest input costs for the beef cattle industry, accounting for 40-60% of the total input costs. Identifying methods for improving feed efficiency in beef cattle herds could result in decreased cost to both producers and consumers, as well as increased animal protein available for global consumption., Methods: In this study, rumen fluid was collected from low- (n = 14) and high-RFI (n = 15) steers. Rumen fluid was filtered through a 0.22 µM syringe filter, extracted using 0.1% formic acid in acetonitrile:water:methanol (2:2:1) and injected into the Dionex UltiMate 3000 UHPLC system with an Exactive Plus Orbitrap MS. Peaks were identified using MAVEN and analyzed using MetaboAnalyst 4.0 and SAS. Significance was determined using an α ≤ 0.05., Results: Eight metabolites were greater in low-RFI steers compared to high-RFI steers, including 3,4-dihydroxyphenylacetate, 4-pyridoxate, citraconate, hypoxanthine, succinate/methylmalonate, thymine, uracil, and xylose (P ≤ 0.05). These metabolites were predominantly involved in amino acid and lipid metabolism., Conclusions: Rumen fluid metabolomes differ in steers of varying feed efficiencies. These metabolites may be used as biomarkers of feed efficiency, and may provide insight as to factors contributing to differences in feed efficiency that may be exploited to improve feed efficiency in beef cattle herds.

The rumen microbiome is critical to nutrient utilization and feed efficiency in cattle. Consequently, the objective of this study was to identify microbial and biochemical factors in Angus steers affecting divergences in feed efficiency using 16S amplicon sequencing and untargeted metabolomics. Based on calculated average residual feed intake (RFI), steers were divided into high- and low-RFI groups. Features were ranked in relation to RFI through supervised machine learning on microbial and metabolite compositions. Residual feed intake was associated with several features of the bacterial community in the rumen. Decreased bacterial α- (P = 0.03) and β- diversity (P < 0.001) was associated with Low-RFI steers. RFI was associated with several serum metabolites. Low-RFI steers had greater abundances of pantothenate (P = 0.02) based on fold change (high/low RFI). Machine learning on RFI was predictive of both rumen bacterial composition and serum metabolomic signature (AUC ≥ 0.7). Log-ratio proportions of the bacterial classes Flavobacteriia over Fusobacteriia were enriched in low-RFI steers (F = 6.8, P = 0.01). Reductions in Fusobacteriia and/or greater proportions of pantothenate-producing bacteria, such as Flavobacteriia, may result in improved nutrient utilization in low-RFI steers. Flavobacteriia and Pantothenate may potentially serve as novel biomarkers to predict or evaluate feed efficiency in Angus steers.

Various separation and mass spectrometric (MS) techniques have furthered our ability to study complex mixtures, and the desire to measure every analyte in a system is of continual interest. For many complex mixtures, such as the total molecular content of a cell, it is becoming apparent that no one single separation technique or analysis is likely to achieve this goal. Therefore, having a variety of tools to measure the complexity of these mixtures is prudent. Orbitrap MSs are broadly used in systems biology studies due to their unique performance characteristics. However, GC-Orbitraps have only recently become available, and instruments that can use gas chromatography (GC) cannot use liquid chromatography (LC) and vice versa. This limits small molecule analyses, such as those that would be employed for metabolomics, lipidomics, or toxicological studies. Thus, a simple, temporary interface was designed for a GC and Thermo Scientific™ Ion Max housing unit. This interface enables either GC or LC separation to be used on the same MS, an Exactive™ Plus Orbitrap, and utilizes an atmospheric pressure chemical ionization (APCI) source. The GC-APCI interface was tested against a commercially available atmospheric pressure photoionization (APPI) interface for three types of analytes that span the breadth of typical GC analyses: fatty acid methyl esters (FAMEs), polyaromatic hydrocarbons (PAHs), and saturated hydrocarbons. The GC-APCI-Orbitrap had similar or improved performance to the APPI and other reported methods in that it had a lower limit of quantitation, better signal to noise, and lower tendency to fragment analytes.

The use of urea as a nitrogenous fertilizer has increased over the past two decades, with urea itself being readily detected at high concentrations in many lakes. Urea has been linked to cyanobacterial blooms as it is a readily assimilated nitrogen (N) - source for cyanobacteria that possess the enzyme urease. We tested the hypothesis that urea may also act as a carbon (C) source to supplemental growth requirements during the alkaline conditions created by dense cyanobacterial blooms, when concentrations of dissolved CO 2 are vanishingly low. High rates of photosynthesis markedly reduce dissolved CO 2 concentrations and drive up pH. This was observed in Lake Erie during the largest bloom on record (2015) over long periods (months) and short periods (days) of time, suggesting blooms experience periods of CO 2 -limitation on a seasonal and daily basis. We used 13 C-urea to demonstrate that axenic cultures of the model toxic cyanobacterium, Microcystis aeruginosa NIES843, assimilated C at varying environmentally relevant pH conditions directly into a spectrum of metabolic pools during urea hydrolysis. Primarily, 13 C from urea was assimilated into central C metabolism and amino acid biosynthesis pathways, including those important for the production of the hepatotoxin, microcystin, and incorporation into these pathways was at a higher percentage during growth at higher pH. This corresponded to increased growth rates on urea as the sole N source with increasing pH. We propose this ability to incorporate C from urea represents yet another competitive advantage for this cyanobacterium during dense algal blooms.

Amyloidosis is a malignant pathology associated with the formation of proteinaceous amyloid fibrils that deposit in organs and tissues, leading to dysfunction and severe morbidity. More than 25 proteins have been identified as components of amyloid, but the most common form of systemic amyloidosis is associated with the deposition of amyloid composed of Ig light chains (AL). Clinical management of amyloidosis focuses on reducing synthesis of the amyloid precursor protein. However, recently, passive immunotherapy using amyloid fibril-reactive antibodies, such as 11-1F4, to remove amyloid from organs has been shown to be effective at restoring organ function in patients with AL amyloidosis. However, 11-1F4 does not bind amyloid in all AL patients, as evidenced by PET/CT imaging, nor does it efficiently bind the many other forms of amyloid. To enhance the reactivity and expand the utility of the 11-1F4 mAb as an amyloid immunotherapeutic, we have developed a pretargeting "peptope" comprising a multiamyloid-reactive peptide, p5+14, fused to a high-affinity peptide epitope recognized by 11-1F4. The peptope, known as p66, bound the 11-1F4 mAb in vitro with subnanomolar efficiency, exhibited multiamyloid reactivity in vitro and, using tissue biodistribution and SPECT imaging, colocalized with amyloid deposits in a mouse model of systemic serum amyloid A amyloidosis. Pretreatment with the peptope induced 11-1F4 mAb accumulation in serum amyloid A deposits in vivo and enhanced 11-1F4-mediated dissolution of a human AL amyloid extract implanted in mice., Competing Interests: Conflict of interest statement: J.S.W., J.S.F., and S.J.K. are named inventors on a Patent Cooperation Treaty patent application that describes the use of peptope technology.

The environmental impacts of hydraulic fracturing, particularly those of surface spills in aquatic ecosystems, are not fully understood. The goals of this study were to (1) understand the effect of previous exposure to hydraulic fracturing fluids on aquatic microbial community structure and (2) examine the impacts exposure has on biodegradation potential of the biocide glutaraldehyde. Microcosms were constructed from hydraulic fracturing-impacted and nonhydraulic fracturing-impacted streamwater within the Marcellus shale region in Pennsylvania. Microcosms were amended with glutaraldehyde and incubated aerobically for 56 days. Microbial community adaptation to glutaraldehyde was monitored using 16S rRNA gene amplicon sequencing and quantification by qPCR. Abiotic and biotic glutaraldehyde degradation was measured using ultra-performance liquid chromatography--high resolution mass spectrometry and total organic carbon. It was found that nonhydraulic fracturing-impacted microcosms biodegraded glutaraldehyde faster than the hydraulic fracturing-impacted microcosms, showing a decrease in degradation potential after exposure to hydraulic fracturing activity. Hydraulic fracturing-impacted microcosms showed higher richness after glutaraldehyde exposure compared to unimpacted streams, indicating an increased tolerance to glutaraldehyde in hydraulic fracturing impacted streams. Beta diversity and differential abundance analysis of sequence count data showed different bacterial enrichment for hydraulic fracturing-impacted and nonhydraulic fracturing-impacted microcosms after glutaraldehyde addition. These findings demonstrated a lasting effect on microbial community structure and glutaraldehyde degradation potential in streams impacted by hydraulic fracturing operations.

In Salmonella enterica , aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. When purH is eliminated in an otherwise wild-type strain, AICAR accumulates and indirectly inhibits synthesis of the essential coenzyme thiamine pyrophosphate (TPP). In this study, untargeted metabolomics approaches were used to i) corroborate previously defined metabolite changes, ii) define the global consequences of AICAR accumulation and iii) investigate the metabolic effects of mutations that restore thiamine prototrophy to a purH mutant. The data showed that AICAR accumulation led to an increase in the global regulator cyclic AMP (cAMP) and that disrupting central carbon metabolism could decrease AICAR and/or cAMP to restore thiamine synthesis. A mutant ( icc ) blocked in cAMP degradation that accumulated cAMP but had wild-type levels of AICAR was used to identify changes in the purH metabolome that were a direct result of elevated cAMP. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell., Competing Interests: Conflict of interest: The authors have no conflict of interest to declare.

The trophic linkage between marine bacteria and phytoplankton in the surface ocean is a key step in the global carbon cycle, with almost half of marine primary production transformed by heterotrophic bacterioplankton within hours to weeks of fixation. Early studies conceptualized this link as the passive addition and removal of organic compounds from a shared seawater reservoir. Here, we analysed transcript and intracellular metabolite patterns in a two-member model system and found that the presence of a heterotrophic bacterium induced a potential recognition cascade in a marine phytoplankton species that parallels better-understood vascular plant response systems. Bacterium Ruegeria pomeroyi DSS-3 triggered differential expression of >80 genes in diatom Thalassiosira pseudonana CCMP1335 that are homologs to those used by plants to recognize external stimuli, including proteins putatively involved in leucine-rich repeat recognition activity, second messenger production and protein kinase cascades. Co-cultured diatoms also downregulated lipid biosynthesis genes and upregulated chitin metabolism genes. From differential expression of bacterial transporter systems, we hypothesize that nine diatom metabolites supported the majority of bacterial growth, among them sulfonates, sugar derivatives and organic nitrogen compounds. Similar recognition responses and metabolic linkages as observed in this model system may influence carbon transformations by ocean plankton., (© 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Black band disease (BBD) of corals is a horizontally migrating, pathogenic, polymicrobial mat community which is active above a temperature threshold of 27.5°C on the reef. Bacterial isolates from BBD, the surface mucopolysaccharide layer (SML) of healthy corals and SML of healthy areas of BBD-infected corals were tested for production of short- to medium-chain acyl homoserine lactones (AHLs) using the Chromobacterium violaceum CV026 reporter strain. Of 110 bacterial isolates tested, 19 produced AHLs and 15 of these were from BBD. Eight AHLs were identified using LC-MS/MS, with 3OHC4 the most commonly produced, followed by C6. AHL-producing isolates exposed to three temperatures (24°C, 27°C, 30°C) revealed that production of three AHLs (3OHC4, 3OHC5 and 3OHC6) significantly increased at 30°C when compared to 24°C. 16S rRNA gene sequencing revealed that all of the AHL-producing BBD isolates were vibrios. Metagenomic data of BBD communities showed the presence of AHL (and autoinducer-2) genes, many of which are known to be associated with vibrios. These findings suggest that quorum sensing may be involved in BBD pathobiology and community structure due to enhanced production of quorum-sensing signal molecules (AHLs) above the temperature threshold of this globally distributed coral disease., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.

About half the carbon fixed by phytoplankton in the ocean is taken up and metabolized by marine bacteria, a transfer that is mediated through the seawater dissolved organic carbon (DOC) pool. The chemical complexity of marine DOC, along with a poor understanding of which compounds form the basis of trophic interactions between bacteria and phytoplankton, have impeded efforts to identify key currencies of this carbon cycle link. Here, we used transcriptional patterns in a bacterial-diatom model system based on vitamin B12 auxotrophy as a sensitive assay for metabolite exchange between marine plankton. The most highly up-regulated genes (up to 374-fold) by a marine Roseobacter clade bacterium when cocultured with the diatom Thalassiosira pseudonana were those encoding the transport and catabolism of 2,3-dihydroxypropane-1-sulfonate (DHPS). This compound has no currently recognized role in the marine microbial food web. As the genes for DHPS catabolism have limited distribution among bacterial taxa, T. pseudonana may use this sulfonate for targeted feeding of beneficial associates. Indeed, DHPS was both a major component of the T. pseudonana cytosol and an abundant microbial metabolite in a diatom bloom in the eastern North Pacific Ocean. Moreover, transcript analysis of the North Pacific samples provided evidence of DHPS catabolism by Roseobacter populations. Other such biogeochemically important metabolites may be common in the ocean but difficult to discriminate against the complex chemical background of seawater. Bacterial transformation of this diatom-derived sulfonate represents a previously unidentified and likely sizeable link in both the marine carbon and sulfur cycles.