Biology subjects

Carlson, C. M.

Publications and source records attributed to Carlson, C. M..

6 recordsLinked to original sources

bioRxiv2026

Bioactive Natural Products Produced by Streptomyces from the Microbiome of Cadaveric Fly Larvae

Streptomyces are prolific producers of bioactive compounds and increasingly recognized as members of insect microbiomes, yet the microbiome of cadaveric fly larvae remain an overlooked system for discovering metabolically versatile Streptomyces species. Here, we conduct targeted bacterial isolations from the microbiome of fly larvae collected from pig cadavers, generating 42 Streptomyces isolates of interest, and systematically evaluated their metabolic potential through genomic analysis, antimicrobial screening, biosynthetic gene cluster assessment, untargeted LC-MS/MS metabolomics, and compound purification. The Streptomyces isolates spanned nine species, including underrepresented lineages for which we added genomic representatives. Streptomyces from carrion fly larvae exhibited broad-spectrum antimicrobial activity and substantial BGC diversity, supported by metabolomic detection of antimycins, surugamides, and macrotetrolides. From a deep phylogenetic lineage, we purified JBIR-68 and Simamycin and demonstrated their potent anthelmintic activity against Brugia malayi microfilariae. GNPS molecular networking revealed three additional JBIR-68 analogs, establishing the first taxonomically resolved Streptomyces lineage capable of producing these rare metabolites. Our findings position cadaveric fly larvae as a rich ecological reservoir for discovering Streptomyces with the potential to produce chemically diverse natural products with biomedical applications.

biochemistry↗

bioRxiv2024

Large-scale investigation for antimicrobial activity reveals novel defensive species across the healthy skin microbiome

The human skin microbiome constitutes a dynamic barrier that can impede pathogen invasion by producing antimicrobial natural products. Gene clusters encoding for production of secondary metabolites, biosynthetic gene clusters (BGCs), that are enriched in the human skin microbiome relative to other ecological settings, position this niche as a promising source for new natural product mining. Here, we introduce a new human microbiome isolate collection, the EPithelial Isolate Collection (EPIC). It includes a large phylogenetically diverse set of human skin-derived bacterial strains from eight body sites. This skin collection, consisting of 980 strains is larger and more diverse than existing resources, includes hundreds of rare and low-abundance strains, and hundreds of unique BGCs. Using a large-scale co-culture screen to assess 8,756 pairwise interactions between skin-associated bacteria and potential pathogens, we reveal broad antifungal activity by skin microbiome members. Integrating 287 whole isolate genomes and 268 metagenomes from sampling sites demonstrates that while the distribution of BGC types is stable across body sites, specific gene cluster families (GCFs), each predicted to encode for a distinct secondary metabolite, can substantially vary. Sites that are dry or rarely moist harbor the greatest potential for discovery of novel bioactive metabolites. Among our discoveries are four novel bacterial species, three of which exert significant and broad-spectrum antifungal activity. This comprehensive isolate collection advances our understanding of the skin microbiomes biosynthetic capabilities and pathogen-fighting mechanisms, opening new avenues towards antimicrobial drug discovery and microbiome engineering.

microbiology↗

bioRxiv2021

Weakly migratory metastatic breast cancer cells activate fibroblasts via microvesicle-Tg2 to facilitate dissemination and metastasis

Cancer cell migration is highly heterogeneous, and the migratory capability of cancer cells is thought to be an indicator of metastatic potential. It is becoming clear that a cancer cell does not have to be inherently migratory to metastasize, with weakly migratory cancer cells often found to be highly metastatic. However, the mechanism through which weakly migratory cells escape from the primary tumor remains unclear. Here, utilizing phenotypically sorted highly and weakly migratory breast cancer cells, we demonstrate that weakly migratory metastatic cells disseminate from the primary tumor via communication with stromal cells. While highly migratory cells are capable of single cell migration, weakly migratory cells rely on cell-cell signaling with fibroblasts to escape the primary tumor. Weakly migratory cells release microvesicles rich in tissue transglutaminase 2 (Tg2) which activate fibroblasts and lead weakly migratory cancer cell migration in vitro. These microvesicles also induce tumor stiffening and fibroblast activation in vivo and enhance the metastasis of weakly migratory cells. Our results identify microvesicles and Tg2 as potential therapeutic targets for metastasis and reveal a novel aspect of the metastatic cascade in which weakly migratory cells release microvesicles which activate fibroblasts to enhance cancer cell dissemination.

cancer biology↗

bioRxiv2020

Biomineral armor in leaf-cutter ants

Although calcareous anatomical structures have evolved in diverse animal groups, such structures have been unknown in insects. Here, we report the discovery of high-magnesium calcite [CaMg(CO3)2] armor overlaying the exoskeletons of major workers of the leaf-cutter ant Acromyrmex echinatior. Live-rearing and in vitro synthesis experiments indicate that the biomineral layer accumulates rapidly as ant workers mature, that the layer is continuously distributed, covering nearly the entire integument, and that the ant epicuticle catalyzes biomineral nucleation and growth. In situ nanoindentation demonstrates that the biomineral layer significantly hardens the exoskeleton. Increased survival of ant workers with biomineralized exoskeletons during aggressive encounters with other ants and reduced infection by entomopathogenic fungi demonstrate the protective role of the biomineral layer. The discovery of biosynthesized high-magnesium calcite in the relatively well-studied leaf-cutting ants suggests that calcareous biominerals enriched in magnesium may be more common in metazoans than previously recognized.

biophysics↗

bioRxiv2019

Cycloheximide-Producing Streptomyces Associated with Xyleborinus saxesenii and Xyleborus affinis Fungus-Farming Ambrosia Beetles

Symbiotic microbes help a myriad of insects acquire nutrients. Recent work suggests that insects also frequently associate with actinobacterial symbionts that produce molecules to help defend against parasites and predators. Here we explore a potential association between Actinobacteria and two species of fungus-farming ambrosia beetles, Xyleborinus saxesenii and Xyleborus affinis. We isolated and identified actinobacterial and fungal symbionts from laboratory reared nests, and characterized small molecules produced by the putative actinobacterial symbionts. One 16S rRNA phylotype of Streptomyces (XylebKG-1) was abundantly and consistently isolated from the nests and adults of X. saxesenii and X. affinis nests. In addition to Raffaelea sulphurea, the symbiont that X. saxesenii cultivates, we also repeatedly isolated a strain of Nectria sp. that is an antagonist of this mutualism. Inhibition bioassays between S. griseus XylebKG-1 and the fungal symbionts from X. saxesenii revealed strong inhibitory activity of the actinobacterium towards the fungal antagonist Nectria sp. but not the fungal mutualist R. sulphurea. Bioassay guided HPLC fractionation of S. griseus XylebKG-1 culture extracts, followed by NMR and mass spectrometry identified cycloheximide as the compound responsible for the observed growth inhibition. A biosynthetic gene cluster putatively encoding cycloheximide was also identified in S. griseus XylebKG-1. The consistent isolation of a single 16S phylotype of Streptomyces from two species of ambrosia beetles, and our finding that a representative isolate of this phylotype produces cycloheximide, which inhibits a parasite of the system but not the cultivated fungus, suggests that these actinobacteria may play defensive roles within these systems.

microbiology↗

bioRxiv2018

Bacterial competition mediated by siderophore production among the human nasal microbiota

Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed co-culture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that Staphylococcus epidermidis isolates were sensitive to growth inhibition by Actinobacteria but Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit S. epidermidis. We sequenced the genomes of ten Corynebacterium spp. isolates, including three Corynebacterium propinquum that strongly inhibited S. epidermidis and seven other Corynebacterium spp. isolates that only weakly inhibited S. epidermidis. Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and encoded a biosynthetic gene cluster (BGC) for siderophore production, absent in the non-inhibitory Corynebacterium spp. genomes. Using a chromeazurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued S. epidermidis from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Using comparative metabolomics, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project.\n\nTogether, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.\n\nIMPORTANCEWithin the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus spp. strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and post-translationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by depleting access to essential nutrients. As the nasal cavity is a nutrient limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore and is able to use this molecule to sequester iron and inhibit the growth of Staphylococcus epidermidis. Further, we found that the genes required for siderophore production are expressed in vivo. Thus, though siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.

microbiology↗