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Caraballo Rodriguez, A. M.

Publications and source records attributed to Caraballo Rodriguez, A. M..

6 recordsLinked to original sources

The caddisfly gut microbiome contributes to the consumption of riparian leaf litter within rivers

Ecosystem functions can be regulated by biodiversity ranging from broad to narrow scales, including variation within a species. For most multicellular life, intraspecific variation is determined not only by an organism's phenotype and genotype, but also variation imparted by their microbiome. Here, we investigate how leaf decomposition in rivers is affected by phenotypic variation in plant secondary metabolites (PSMs) and antibiotic-induced variation within the gut microbiomes of aquatic macroinvertebrate decomposers. We found that consumption by Dicosmoecus caddisflies was inhibited by the presence of dietary PSMs from riparian Alnus rubra trees, irrespective of the state of their gut microbiome. We further compared consumption of diets prepared from 20 different local and non-local A. rubra trees. We found that antibiotic-treated and control caddisflies consumed similar amounts of diets containing local A. rubra PSMs. However, compared to caddisflies with an intact gut microbiome, antibiotic-treated caddisflies consumed less of non-local A. rubra diets. Thus, decomposition by caddisflies could be regulated by both host adaptation to local resources and bacterial-mediated digestion of non-local resources. Overall, our study suggests that gut microbiomes can facilitate adjustment of macroinvertebrate decomposers to novel plant phenotypes, which may arise from shifting spatial distributions of plants in response to global change.

ecology↗

Alkamines reveal a hidden layer of steroid and drug metabolism

Biomedical research overlooks most genes in favor of a well-studied minority, yet whether analogous blind spots exist in metabolomics remains unknown. We show that reductive amination, forming secondary amines from aldehydes or ketones and amines, generates a previously hidden class of metabolites we term alkamines. Multiplexed synthesis of 8,475 alkamines combined with MS/MS searches across 1.7 billion spectra identified 1,626 candidates across multiple species and organs. Of these, 56 were confirmed in biological samples, including 27 steroid- and 12 drug-derived alkamines matching prescription patterns. Notably, 77% of synthesized alkamines are absent from PubChem. This combinatorial logic likely explains why alkamines have evaded detection and suggests drug metabolism frameworks substantially underestimate drug-derived metabolite diversity. Reductive amination is an overlooked route modifying steroids, bile acids, and xenobiotics.

biochemistry↗

A searchable metadata network graph for microbiome metabolomics

Establishing the biological context of microbial metabolites remains a major challenge. We present microbiomeMASST, a metadata-driven network graph that maps metabolites across 467 available datasets with 144,424 mass spectrometry files from humans, animals, and microbial culture systems. MicrobiomeMASST integrates monocultures, synthetic communities, and host-associated samples across multiple body sites and plants. MS/MS spectra can be queried to trace occurrence across hosts, experimental conditions, and interventions, enabling cross-study integration. We demonstrate this framework by contextualizing microbial-conjugated bile acids and interrogating microbiome-mediated drug metabolism. Screening gut bacteria revealed deprolylation of the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril. Using microbiomeMASST, we traced this metabolite across human cohorts, microbial isolates, environmental samples, and in Gorilla gorilla. Structural modeling and enzymatic assays showed that microbial deprolylation abolishes ACE inhibition, thereby inactivating its therapeutic effect. Together, microbiomeMASST links MS/MS spectra to biological context, converting isolated observations into an interpretable microbiome map for cross-study analysis.

biochemistry↗

Ecological Interactions Drive Metabolomic Diversification in Amazonian Pseudonocardia Symbionts

Fungus-growing ants engage in a multipartite symbiosis, including Pseudonocardia bacteria that produce antifungal metabolites to protect their fungal cultivar from the specialized pathogen Escovopsis. While different bioactive metabolites have been reported from ant-associated Pseudonocardia, most studies have focused on a limited number of strains, leaving the extent of chemical diversity across broader ecological contexts less resolved. Here, we investigated the antagonistic potential and metabolomic repertoires of 36 Pseudonocardia strains isolated from Amazonian Paratrachymyrmex ants. Pairwise bioactivity assays against two Escovopsis isolates revealed striking variability, with inhibition generally stronger and more diverse against the pathogenic fungus originating from the same ant genus. Untargeted LC-MS/MS metabolomics coupled with 16S rRNA-based phylogenetic analyses showed that closely related strains harbored highly divergent chemical profiles, underscoring a decoupling between taxonomy and metabolite output. Detailed analyses of selected isolates revealed the production of structurally diverse metabolites, including dentigerumycin analogs, provipeptide A, {beta}-carbolines, and tetracycline-related compounds. Co-culture analysis uncovered metabolites absent in monocultures, including lichenysins, pepstatins, and hallobacillins, as well as conserved attinimicin, whose production was enhanced under pathogen challenge. These results highlight that both strain-specific metabolic repertoires and interaction-induced chemistry contribute to the defensive arsenal of Pseudonocardia. Together, our findings likely demonstrate that ecological pressures and local adaptation, rather than phylogeny alone, drive metabolomic diversification in this defensive symbiosis. Beyond their potential for novel bioactive compound discovery, these results provide insights into the chemical basis of multipartite symbioses, the dynamics of defensive mutualisms, and the ecological forces shaping microbial diversity in underexplored environments such as the Amazon. IMPORTANCEMicrobial symbionts are central to host defense and natural product discovery, yet the factors driving their chemical diversification remain unclear. The fungus-growing ant-Pseudonocardia-Escovopsis system offers a powerful model to study how ecological context shapes microbial metabolism. By systematically characterizing multiple Amazonian Pseudonocardia strains, we show that antagonistic capacity and metabolomic repertoires vary widely, even among strains with highly similar 16S rRNA gene sequences, revealing a pronounced discordance between 16S-based phylogenetic relatedness and specialized metabolite production. These findings highlight the likely importance of ecological pressures and local adaptation in shaping metabolomic output, emphasizing symbiotic actinobacteria as both key ecological players and promising sources of antifungal natural products.

microbiology↗

Trachymyrmex septentrionalis ants promote fungus garden hygiene using Trichoderma-derived metabolite cues

Fungus-growing ants depend on a fungal mutualist that can fall prey to fungal pathogens. This mutualist is cultivated by these ants in structures called fungus gardens. Ants exhibit weeding behaviors that keep their fungus gardens healthy by physically removing compromised pieces. However, how ants detect diseases of their fungus gardens is unknown. Here, we applied the logic of Kochs postulates using environmental fungal community gene sequencing, fungal isolation, and laboratory infection experiments to establish Trichoderma spp. as previously unrecognized pathogens of Trachymyrmex septentrionalis fungus gardens. Our environmental data showed that Trichoderma are the most abundant non-cultivar fungi in wild T. septentrionalis fungus gardens. We further determined that metabolites produced by Trichoderma induce an ant weeding response that mirrors their response to live Trichoderma. Combining ant behavioral experiments with bioactivity-guided fractionation and statistical prioritization of metabolites in Trichoderma extracts demonstrated that T. septentrionalis ants weed in response to peptaibols, a specific class of secondary metabolites known to be produced by Trichoderma fungi. Similar assays conducted using purified peptaibols, including the two new peptaibols trichokindins VIII and IX, suggested that weeding is likely induced by peptaibols as a class rather than by a single peptaibol metabolite. In addition to their presence in laboratory experiments, we detected peptaibols in wild fungus gardens. Our combination of environmental data and laboratory infection experiments strongly support that peptaibols act as chemical cues of Trichoderma pathogenesis in T. septentrionalis fungus gardens. Significance StatementAn extended defense response may exist in any relationship where one partner benefits from defending a mutualistic partner. Such a response is observed in the fungus-growing ant symbiosis, where ants must identify and remove pathogens of their symbiotic fungus gardens. Here we describe the fungal pathogen Trichoderma and its associated metabolites, which induce Trachymyrmex septentrionalis ant weeding behavior. Ants removed fungus garden pieces inoculated with Trichoderma spores or peptaibol-rich Trichoderma extracts, and peptaibols as a class cued ant defensive behavior, allowing T. septentrionalis to differentiate healthy from diseased fungus gardens. Extended defense responses mediated by chemical cues may be underappreciated mechanisms that structure symbiotic interactions.

microbiology↗

Open Access Repository-Scale Propagated Nearest Neighbor Suspect Spectral Library for Untargeted Metabolomics

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of public MS/MS spectra. Annotations were propagated based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimers brain phenotype. The nearest neighbor suspect spectral library is openly available through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

bioinformatics↗