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Biology subjects

Marti, G.

Publications and source records attributed to Marti, G..

15 recordsLinked to original sources

A Galbonolide producing Streptomyces reconfigures the plant root microbiota by activating salicylate-dependent defence metabolism

Streptomyces sp. AgN23 is an epiphytic rhizobacterium that establishes in the Arabidopsis rhizosphere by activating plant immune responses. This activity depends on the secretion of polyketide galbonolides, which inhibit host inositol phosphoceramide synthase (IPCS) and thereby perturb sphingolipid homeostasis. However, the downstream signalling events linking IPCS inhibition to AgN23 enrichment in the rhizosphere remain unclear. Here, we show that AgN23 activates ethylene- and salicylic acid-dependent immune signalling, leading to coordinated stimulation of phenylalanine- and tryptophan-derived secondary metabolism. Using Arabidopsis mutants defective in these pathways, we show that these metabolites mitigate AgN23-induced root growth inhibition. We further show that the npr1 mutant is strongly compromised in AgN23-triggered secondary metabolic responses, resulting in reduced rhizosphere colonization by AgN23. By comparing rhizosphere microbiota from wild-type and npr1 plants, we distinguished direct AgN23 effects linked to intermicrobial competition from indirect effects mediated by host metabolic activation. In particular, AgN23 colonization occurred at the expense of several Streptomycetaceae ASVs and coincided with changes in bacterial and fungal taxa belonging to Flavobacteriaceae and Mucoromycota. Together, these findings define a mechanistic framework in which Streptomyces AgN23 interacts with NPR1-dependent signalling to reprogram root metabolism and rhizosphere community structure, notably through the production of specialized metabolites such as galbonolides.

plant biology↗

A fatal plant toxicosis described more than a century ago is caused by a bacterial endophyte

Gousiekte ( quick disease) is a fatal plant toxicosis affecting livestock in South Africa. Gousiekte is characterized by the sudden death of animals following the ingestion of leaves of several species of Rubiaceae, most notably Vangueria pygmaea, Pavetta harborii, P. schumanniana and Fadogia homblei. The toxin causing gousiekte is pavettamine, a hydroxylated polyamine pavettamine for which no biosynthetic pathway is known. Interestingly, all plants known to contain pavettamine also feature obligate endophytes of the Burkholderiaceae family, in particular belonging to the Caballeronia and Paraburkholderia genera. We identified a cluster of three genes conserved in all Burkholderia s.l. endophytic symbionts of plants containing pavettamine. Constitutive expression the pavABC gene cluster in a strain of Paraburkholderia caledonica isolated from leaves of Fadogia homblei resulted in detectable levels of pavettamine in cultures, and targeted gene deletions showed the involvement of all three genes in its biosynthesis. Genomes of important animal and human pathogens of the Burkholderia pseudomallei complex encode functional homologs of the pavABC genes, indicating a potentially unrecognized role of pavettamine in disease or complications from infections. Significance statementGousiekte is a fatal disease of livestock caused by plants containing the toxin pavettamine, yet the origin of this compound has remained a mystery. We demonstrate that pavettamine is synthesized not by the plants themselves, but by their obligate bacterial endophytes via a conserved three-gene cluster, pavABC. Crucially, these genes were likely acquired via horizontal gene transfer from an ancestor of the Burkholderia pseudomallei complex, a group of significant human and animal pathogens. This discovery identifies the genetic basis of a potent toxin and suggests a previously unrecognized role for pavettamine in human infectious diseases. This work emphasizes the preeminent role of horizontal gene transfer and secondary metabolism for host-microbe interactions.

microbiology↗

Stage-resolved metabolomics reveals the methionine cycle as a key regulator of Aedes aegypti development and dengue virus susceptibility

Developmental transitions in the mosquito Aedes aegypti are central to vector competence and disease transmission, yet the underlying metabolic programs remain poorly defined. Here, we use untargeted metabolomics, gene expression analysis, and functional assays to delineate stage-specific metabolic fingerprints across the mosquito life cycle, from egg and larva to pupa and adult. Our profiling of the larval diet reveals comprehensive provisioning of essential nutrients, including B vitamins critical for development. Metabolomic analyses uncover distinct, stage-specific signatures, with the larval stage exhibiting a pronounced enrichment of methionine cycle metabolites and maximal methylation capacity. Notably, while S-adenosylmethionine (SAM) and related metabolites peak in larvae, the transcription of the methionine cycle and histone methyltransferase genes is highest in adults. Functional disruption of the methionine cycle in mosquito cells reveals network-level robustness and regulatory crosstalk within the pathway. However, we also identify a specific vulnerability: silencing the gene adenosylhomocysteinase (ahcy) enhances dengue virus 1 replication and infectious particle production. Collectively, our findings identify the methionine cycle as a metabolic-epigenetic hub that integrates nutrition, development, and viral susceptibility, and highlight the larval stage as a strategic target for novel mosquito-control strategies.

microbiology↗

Artificial symbiont replacement in a vertically-transmitted plant-bacterium association provides insights into the basis for specificity

Some plants engage in permanent, vertically transmitted symbioses with bacteria. Often, these bacteria are hosted extracellularly in specific structures on the leaves, where they produce specialized bioactive metabolites that benefit their host. These associations are highly specific, with one plant species associating with a single bacterial species, but little is known about how these symbioses originate and how specificity is maintained. In this study, we show that the symbiotic association between a wild yam and a bacterium can be manipulated experimentally, and that bacteria-free plants are open to colonization by environmental bacteria. Through metabolic profiling, we show that the endophytic niche is rich in organic acids and intermediates of the TCA cycle. Environmental bacteria capable of utilizing these acids, such as the soil bacterium Pseudomonas putida, readily colonize aposymbiotic plants. However, successful colonization is contingent upon the absence of the vertically-transmitted symbiont and an active type VI secretion system. Unexpectedly for a vertically-transmitted symbiosis, these findings suggest that microbe-microbe interactions, including antagonism, may play a crucial role in maintaining the specificity of an association. However, low transmission rates of synthetic symbionts provide evidence that transmission barriers or bottlenecks may still occur, further enforcing partner fidelity. Together, these results highlight the complexity of mechanisms underlying mutualistic associations, and provide insights into the evolution of bacterial leaf symbiosis.

microbiology↗

An Independent Coding Scheme for Distance versus Position in the Hippocampus

Animals navigate using cognitive maps of their environment, integrating external landmarks and distances between them. Hippocampal place cells are the neuronal substrate of these cognitive maps. However, while hippocampal allocentric position coding in reference to external landmarks is well characterized, the determinants of idiothetic hippocampal distance coding remain poorly understood. Using virtual reality, electrophysiological recordings in mice, and local cue manipulations we could dissociate distance from position coding. In the cue-poor condition, we found pervasive distance coding with high distance indices in all bidirectional place cells including both superficial and deep CA1 pyramidal cells. In this condition, the mapping of distance onto a low-dimensional manifold and rigid distance relationships between place fields suggested strong attractor dynamics similar to those observed for grid cells. Inactivation of the medial septum (MS), which disrupts grid cells, significantly reduced both distance coding and rigid distance dynamics, suggesting an alteration (but not complete abolition) of the underlying attractor. In contrast, allocentric position coding could be observed in cue-rich environments, predominantly engaged deep CA1 pyramidal cells, and persisted during MS inactivation. These results are consistent with a selective contribution of grid cells and associated rigid attractor dynamics to hippocampal idiothetic distance coding but not allocentric position coding.

neuroscience↗

Single-cell transcriptional landscapes of Aedes aegypti midgut and fat body after a bloodmeal

Aedes aegypti mosquitoes are vectors for numerous arboviruses that have an increasingly substantial global health burden. Following a bloodmeal, mosquitoes experience significant physiological changes, primarily orchestrated by the midgut and fat body tissues. These changes begin with digestion and culminate in egg production. However, our understanding of those key processes at the cellular and molecular level remains limited. We have created a comprehensive cell atlas of the mosquito midgut and fat body by employing single-cell RNA sequencing and metabolomics techniques. This atlas unveils the dynamic cellular composition and metabolic adaptations that occur following a bloodmeal. Our analyses reveal highly diverse cell populations, specialized in digestion, metabolism, immunity, and reproduction. While the midgut primarily comprises enterocytes, enteroendocrine and intestinal stem cells, the fat body consists not only of trophocytes and oenocytes, but also harbors a substantial hemocyte population and a newly found fat body-yolk cell population. The fat body exhibits a complex cellular and metabolomic profile and exerts a central role in coordinating immune and metabolic processes. Additionally, an insect-specific virus, PCLV (Phasi Charoen-Like Virus) was detected in single cells, mainly in the midgut a week after the bloodmeal. These findings highlight the complexity of the mosquitos abdominal tissues, and pave the way towards the development of exquisitely refined vector control strategies consisting of genetically targeting specific cell populations and metabolic pathways necessary for egg development after a bloodmeal.

cell biology↗

Sphingomyelins in mosquito saliva modify the host lipidome to enhance transmission of flaviviruses by promoting viral protein levels

Mosquito saliva plays a determining role in flavivirus transmission. Here, we discover and elucidate how salivary lipids enhance transmission. Building upon our discovery of salivary extracellular vesicles (EV), we determined that lipids within mosquito EVs, and neither within human EVs nor virions, enhance infection for flaviviruses in primary cell types relevant for transmission. Mechanistically, mosquito EV-lipids specifically promote viral protein levels by reducing ER-associated degradation. Infection enhancement is caused by sphingomyelins within mosquito salivary EVs that elevate sphingomyelin concentration within host cells. Transmission assays showed that mosquito EV-lipids exacerbate disease severity. Our study reveals that EV-associated sphingomyelins within mosquito saliva enhance transmission for multiple flaviviruses by reconfiguring the host lipidome to promote viral protein levels and the resulting skin infection. Our findings open a new dimension centered on lipids in the interplay between hosts, mosquitoes and flaviviruses that determine transmission, unveiling lipids as a new pan-flavivirus target. HighlightsO_LILipids within mosquito extracellular vesicles (EVs) enhance infection in primary skin and immune cells for multiple flaviviruses. C_LIO_LIMosquito EV-lipids increase flaviviral protein levels by dampening ER-associated degradation. C_LIO_LISphingomyelins within salivary EVs are responsible for the infection enhancement by altering host lipidome. C_LIO_LICo-injection of mosquito EV-lipids exacerbate disease severity. C_LI

pathology↗

Root associated Streptomyces produce galbonolides to modulate plant immunity and promote rhizosphere colonisation

The rhizosphere, which serves as the primary interface between plant roots and the soil, constitutes an ecological niche for a huge diversity of microbial communities. Currently, there is little knowledge on the nature and the function of the different metabolites released by rhizospheric microbes to facilitate colonization of this highly competitive environment. Here, we demonstrate how the production of galbonolides, a group of polyene macrolides that inhibit plant and fungal Inositol Phosphorylceramide Synthase (IPCS), empowers the rhizospheric Streptomyces strain AgN23, to thrive in the rhizosphere by triggering the plants defence mechanisms. Metabolomic analysis of AgN23-inoculated Arabidopsis roots revealed a strong induction in the production of an indole alkaloid, camalexin, which is a major phytoalexin in Arabidopsis. By using a plant mutant compromised in camalexin synthesis, we show that camalexin production is necessary for the successful colonization of the rhizosphere by AgN23. Conversely, hindering galbonolides biosynthesis in AgN23 knock-out mutant resulted in loss of inhibition of IPCS, a deficiency in plant defence activation, notably the production of camalexin, and a strongly reduced development of the mutant bacteria in the rhizosphere. Together, our results identified galbonolides as important metabolites mediating rhizosphere colonisation by Streptomyces. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/576418v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1ec39f3org.highwire.dtl.DTLVardef@1d0a14eorg.highwire.dtl.DTLVardef@e1f61org.highwire.dtl.DTLVardef@12e487e_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Model summarizing the mode of action of galbonolides in stimulating plant defence to support AgN23 colonization of the rhizosphere. Galbonolides secretion by Streptomyces sp. AgN23 trigger Inositol Phosphoceramide Synthase (IPCS) inhibition in Arabidopsis root cells (orange arrow). The resulting raise in Ceramide precursors of the IPCS may result in the different defence responses associated to AgN23: Hypersensitive Responses (HR), Salicylic Acid (SA) signalling, nuclear Ca2+ influx, defence gene expression and camalexin biosynthesis. This production of camalexin (blue arrow) exert a positive effect on AgN23 growth in the rhizosphere, presumably by restricting the growth of bacterial and fungal competitors sensitive to this phytoalexin. In addition, galbonolides secretion in the rhizosphere may also directly interfere with fungal competitors of AgN23. C_FIG

microbiology↗

Deciphering anti-infectious compounds from Peruvian medicinal Condocillos extract library through multiplexed assays and chemical profiling

High prevalence of parasitic or bacterial infectious diseases in some world areas is due to multiple reasons, including a lack of an appropriate health policy, challenging logistics and poverty. The support to research and development of new medicines to fight infectious diseases is one of the sustainable development goals promoted by World Health Organization (WHO). In this sense, the traditional medicinal knowledge substantiated by ethnopharmacology is a valuable starting point for drug discovery. This work aims at the scientific validation of the traditional use of Piper species ("Cordoncillos") as firsthand anti-infectious medicines. For this purpose, we adapted a computational statistical model to correlate the LCMS chemical profiles of 54 extracts from 19 Piper species to their corresponding anti-infectious assay results based on 37 microbial or parasites strains. We mainly identified two groups of bioactive compounds (called features as they are considered at the analytical level and are not formally isolated). Group 1 is composed of 11 features being highly correlated to an inhibiting activity on 21 bacteria (principally Gram-positive strains), one fungus (C. albicans), and one parasite (Trypanosoma brucei gambiense). The group 2 is composed of 9 features having a clear selectivity on Leishmania (all strains, both axenic and intramacrophagic). Bioactive features in group 1 were identified principally in the extracts of Piper strigosum and P. xanthostachyum. In group 2, bioactive features were distributed in the extracts of 14 Piper species. This multiplexed approach provided a broad picture of the metabolome as well as a map of compounds putatively associated to bioactivity. To our knowledge, the implementation of this type of metabolomics tools aimed at identifying bioactive compounds has not been used so far.

biochemistry↗

Cyclitol secondary metabolism is a central feature of Burkholderia leaf symbionts

The symbioses between plants of the Rubiaceae and Primulaceae families with Burkholderia bacteria represent unique and intimate plant-bacterial relationships. Many of these interactions have been identified through PCR-dependent typing methods, but there is little information available about their functional and ecological roles. We assembled seventeen new endophyte genomes representing endophytes from thirteen plant species, including those of two previously unknown associations. Genomes of leaf endophytes belonging to Burkholderia s.l. show extensive signs of genome reduction, albeit to varying degrees. Except for one endophyte, none of the bacterial symbionts could be isolated on standard microbiological media. Despite their taxonomic diversity, all endophyte genomes contained gene clusters linked to the production of specialized metabolites, including genes linked to cyclitol sugar analog metabolism and in one instance non-ribosomal peptide synthesis. These genes and gene clusters are unique within Burkholderia s.l. and are likely horizontally acquired. We propose that the acquisition of secondary metabolite gene clusters through horizontal gene transfer is a prerequisite for the evolution of a stable association between these endophytes and their hosts.

microbiology↗

Metabotyping of Andean pseudocereals and characterization of emerging mycotoxins

Pseudocereals are best known for three crops derived from the Andes: quinoa (Chenopodium quinoa, Chenopods I), canihua (C. pallidicaule, Chenopods I), and kiwicha (Amaranthus caudatus). Their grains are recognized for their nutritional benefits; however, there is a higher level of polyphenism and the chemical foundation that would rely with such polyphenism has not been thoroughly investigated. Meanwhile, the chemical food safety of pseudocereals remains poorly documented. Here we applied untargeted and targeted metabolomics approach by LC-MS to achieve both: i) a comprehensive chemical mapping of pseudocereal samples collected in the Andes to classify them according to their chemotype; ii) a quantification of their contents in emerging mycotoxins. An inventory of the fungal community was also realized with the aims to better know the filamentous fungi present in these grains and try to parallel this information with the presence of the molecules produced, especially mycotoxins. Metabotyping permitted to add new insights into the chemotaxonomy of pseudocereals, confirming the previously established phylotranscriptomic clades: Chenopods I (clusters quinoa and canihua), and Amaranthaceae s.s. (cluster kiwicha). Moreover, we report for the first time the presence of mycotoxins in pseudocereals. Sixteen samples of Peru (out of 27) and one sample from France (out of one) were contaminated with Beauvericin, an emerging mycotoxin. There were several mycotoxigenic fungi detected, including Aspergillus sp., Penicillium sp., and Alternaria sp., but not Fusaria. Highlights{blacksquare} Twenty-seven grain samples of Andean pseudocereals were profiled by LC-HRMS. {blacksquare}Untargeted metabolomics was used to differentiate varieties from the whole metabolome dataset. {blacksquare}Five mycotoxins were quantify using targeted metabolomics. {blacksquare}Sixteen samples of Peru and one sample from France were contaminated with Beauvericin. {blacksquare}An inventory of the fungal community infesting the Andean pseudocereal samples was documented.

biochemistry↗

Cannabinoids vs. whole metabolome: relevance of cannabinomics in analyzing Cannabis varieties

Cannabis sativa has a long history of domestication both for its bioactive compounds and its fibers. This has produced hundreds of varieties, usually characterized in the literature by chemotypes, with {Delta}9-THC and CBD content as the main markers. However, chemotyping could also be done based on minor compounds (phytocannabinoids and others). In this work, a workflow, which we propose to name cannabinomics, combines mass spectrometry of the whole metabolome and statistical analysis to help differentiate C. sativa varieties and deciphering their characteristic markers. By applying this cannabinomics approach to the data obtained from 20 varieties of C. sativa (classically classified as chemotype I, II, or III), we compared the results with those obtained by a targeted quantification of 11 phytocannabinoids. Cannabinomics can be considered as a complementary tool for phenotyping and genotyping, allowing the identification of minor compounds playing a key role as markers of differentiation.

biochemistry↗

MS-CleanR: A feature-filtering approach to improve annotation rate in untargeted LC-MS based metabolomics

Untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) is currently the gold-standard technique to determine the full chemical diversity in biological samples. This approach still has many limitations, however; notably, the difficulty of estimating accurately the number of unique metabolites being profiled among the thousands of MS ion signals arising from chromatograms. Here, we describe a new workflow, MS-CleanR, based on the MS-DIAL/MS-FINDER suite, which tackles feature degeneracy and improves annotation rates. We show that implementation of MS-CleanR reduces the number of signals by nearly 80% while retaining 95% of unique metabolite features. Moreover, the annotation results from MS-FINDER can be ranked with respect to database chosen by the user, which improves identification accuracy. Application of MS-CleanR to the analysis of Arabidopsis thaliana grown in three different conditions improved class separation resulting from multivariate data analysis and lead to annotation of 75% of the final features. The full workflow was applied to metabolomic profiles from three strains of the leguminous plant Medicago truncatula that have different susceptibilities to the oomycete pathogen Aphanomyces euteiches; a group of glycosylated triterpenoids overrepresented in resistant lines were identified as candidate compounds conferring pathogen resistance. MS-CleanR is implemented through a Shiny interface for intuitive use by end-users (available at: https://github.com/eMetaboHUB/MS-CleanR).

bioinformatics↗

Mature dentate granule cells show different intrinsic properties depending on the behavioural context of their activation

The dentate gyrus (DG) plays a crucial role in learning, memory and spatial navigation. Only a small fraction of mature dentate granule cells (mDGCs) is active during behavior, while the large majority remains silent. To date, the properties of this active subset of neurons remain poorly investigated. Using fosGFP transgenic mice, we show ex vivo that activated mDGCs, from mice maintained in their home cage, exhibit a marked lower intrinsic excitability compared to the non-activated cells. Remarkably, activated mDGCs, from mice trained in a virtual environment, are more excitable than those from mice maintained in their home cage. Therefore, we show that activated mDGCs display different intrinsic properties and excitable states depending on the context of their activation. We propose that these properties could constitute a neural signature of cell assemblies recruited in different behavioral contexts.

neuroscience↗

Dynamic Control of Hippocampal Spatial Coding Resolution by Local Visual Cues

The ability to flexibly navigate an environment relies on a hippocampal-dependent internal cognitive map. Explored space can be internally mapped at different spatial resolutions. However, whether hippocampal spatial coding resolution can be dynamically controlled within and between environments is unknown. In this work we recorded the firing of hippocampal principal cells in mice navigating virtual reality environments, which differed by the presence of local visual cues (virtual 3D objects). Objects improved spatial coding resolution globally with a higher proportion of place cells, smaller place fields, increased spatial selectivity and stability. Spatial coding resolution was notably enhanced locally near objects and could be rapidly tuned by their manipulations. In the presence of objects, place cells also displayed improved theta phase precession and theta timescale spike coordination. These results suggest that local visual cues can rapidly tune the resolution of the hippocampal mapping system within and between environments.

neuroscience↗