Biology subjects

Pishchany, G.

Publications and source records attributed to Pishchany, G..

6 recordsLinked to original sources

bioRxiv2026

Microbial-associated acylated putrescines as immunomodulatory molecules in inflammatory bowel diseases

The gut microbiota regulates intestinal immunity through metabolite production, yet most disease-associated metabolites remain functionally uncharacterized. In inflammatory bowel diseases (IBD), where the microbial metabolome is profoundly altered, we identify N-acyl putrescines as microbiome-associated metabolites enriched across two independent cohorts. N-oleoylputrescine (NOP) emerges as the primary immunomodulatory candidate, inducing robust transcriptional responses in dendritic cells and colonic organoids. Enterocloster species harboring nonribosomal peptide synthetase gene clusters synthesize NOP, confirmed by isotope-tracing in vitro and germ-free mouse colonization in vivo. NOP suppresses core IBD inflammatory pathways in mouse dendritic cells and human monocytes, reducing signatures of histologic inflammation and therapy non-response. NOP dampens inflammation in four colitis models, decreases myeloid cell NF-{kappa}B activation, and suppresses type 1 immune responses through a T cell-intrinsic mechanism. That NOP accumulates in IBD despite its anti-inflammatory properties reveals a holobiont defense strategy: the gut microbiota deploys immunomodulatory metabolites as a compensatory response to restore homeostasis.

immunology↗

bioRxiv2026

Aerocavin is an antibiotic with potent and specific anti-Neisserial activity

Gonorrhea, caused by N. gonorrhoeae, is a widespread sexually transmitted disease that is becoming resistant to all currently used antibiotics. Therefore, new therapeutics against gonorrhea are desperately needed. Here, we show that a natural product - aerocavin, is highly potent and specific against Neisseria. Aerocavin accumulates in N. gonorrhoeae at high levels and inhibits bacterial RNA polymerase (RNAP) by binding the switch region. Aerocavin resistance mutations evolve in N. gonorrhoeae at a low rate and are absent in clinical isolates. Previously overlooked narrow-spectrum antimicrobials like aerocavin may enable microbiome-sparing treatments of gonorrhea.

microbiology↗

bioRxiv2025

Intelectin-2 is a broad-spectrum antimicrobial lectin

Mammals regulate the localization, composition, and activity of their native microbiota at colonization sites. Lectins residing at these sites influence microbial populations, but their individual functions are often unclear. Intelectins are found in chordates at mucosal barriers, but their functions are not well characterized. We found that mouse intelectin-2 (mItln2) and human intelectin-2 (hItln2) engage and crosslink mucins via carbohydrate recognition. Moreover, both lectins recognize microbes within native microbial communities, including gram-positive and gram-negative isolates from the respiratory and gastrointestinal tracts. This ability to engage mammalian and microbial glycans arises from calcium-coordinated binding of carbohydrate residues within mucus and microbial surfaces. Microbes, but not human cells, bound by mItln2 or hItln2, suffer a loss of viability. These findings underscore the crucial antimicrobial role of mammalian intelectin-2 in mucosal defense, where it plays offensive (microbial killing) and defensive (mucus crosslinking) roles in regulating microbial colonization.

microbiology↗

bioRxiv2022

Lectin-Seq: a method to profile lectin-microbe interactions in native communities

Soluble human lectins are critical components of innate immunity. Genetic models suggest lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins roles in regulating microbiota requires understanding which microbial species they bind within native communities. To profile human lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to human fecal microbiota using mannose-binding lectin (MBL) and intelectin-1 (hItln1). The microbial interactomes of MBL and hItln1 differ in composition and diversity. MBL binding is highly selective for a small subset of species commonly associated with humans. In contrast, hItln1s interaction profile encompasses a broad range of lower-abundance species. Thus, human lectins have evolved to recognize distinct species of commensals, suggesting they directly influence microbiome composition. Lectin-Seq offers a new means of annotating microbial communities. One-Sentence SummarySoluble human lectins bind distinct bacterial species in fecal microbiota.

biochemistry↗

bioRxiv2019

The microbiomes of seven lichen genera reveal host specificity, a reduced core community and potential as source of antimicrobials

The High Andean Paramo ecosystem is a unique neotropical mountain biome considered a diversity and evolutionary hotspot. Lichens, which are complex symbiotic structures that contain diverse commensal microbial communities, are prevalent in Paramos. There they play vital roles in soil formation and mineral fixation. In this study we analyzed the microbiomes of seven lichen genera in two Colombian Paramos using 16S rRNA gene analyses and provide the first description of the bacterial communities associated with Cora and Hypotrachyna lichens. Paramo lichen microbiomes were diverse, and in some cases were distinguished based on the identity of the lichen host. The majority of the lichen-associated microorganisms were not present in all lichens sampled and could be considered transient or specialists. We also uncovered sixteen shared taxa that suggest a core lichen microbiome among this diverse group of lichens, broadening our concept of these symbiotic structures. Additionally, we identified strains producing compounds active against clinically relevant pathogens. These results indicate that lichen microbiomes from the Paramo ecosystem are diverse and host-specific but share a taxonomic core and can be a source of new bacterial taxa and antimicrobials.

microbiology↗

bioRxiv2018

Amycomicin: a potent and specific antibiotic discovered with a targeted interaction screen

The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in the environment, bacteria constantly encounter poor nutrient conditions and interact with neighboring microbial species. In an effort to recapitulate this environment we generated a nine-strain Actinomycete community and used 16S rDNA sequencing to deconvolute the stochastic production of antimicrobial activity that was not observed from any of the axenic cultures. We subsequently simplified the community to just two strains and identified Amycolatopsis sp. AA4 as the producing strain and Streptomyces coelicolor M145 as an inducing strain. Bioassay-guided isolation identified amycomicin, a highly modified fatty acid containing an epoxide isonitrile warhead as a potent and specific inhibitor of Staphylococcus aureus. Amycomicin targets an essential enzyme in fatty acid biosynthesis (FabH) and reduces S. aureus infection in a mouse skin infection model. The discovery of amycomicin demonstrates the utility of screening complex communities against specific targets to discover small-molecule antibiotics.\n\nSignificanceBacteria, especially actinomycetes, produce the majority of our clinically useful small-molecule antibiotics. Genomic analyses of antibiotic-producing strains indicate that earlier discovery efforts found only a fraction of the likely antibiotic candidates. In an effort to uncover these previously missed candidates we developed an approach that utilizes the ability of microbial communities to produce antibiotics that are not produced by any single member in isolation. Successful communities were established and deconvoluted to identify both producers and inducers of antibiotic activity. One inducer-producer pair made amycomicin, a potent and specific antibiotic against Staphylococcus aureus, an important human pathogen. Amycomicin targets fatty acid biosynthesis and exhibits in vivo efficacy against skin infections in a mouse model.

microbiology↗