Biology subjects

Luzzatto-Knaan, T.

Publications and source records attributed to Luzzatto-Knaan, T..

6 recordsLinked to original sources

bioRxiv2026

MetaboCensoR: A Shiny Application for Data Filtering in Untargeted LC-MS Metabolomics to Enhance Interpretability

Untargeted LC-MS metabolomics datasets often contain large numbers of redundant and non-informative features arising from background contaminants, multiple ion forms, poorly integrated peaks, and other low-quality signals. These features complicate downstream analysis by inflating feature space, degrading molecular networks, impeding pathway analysis, and obscuring statistically meaningful changes. Here, we present MetaboCensoR, an input-versatile Shiny application and local R package that bridges the gap between LC-MS peak picking and downstream interpretation through analyte-centric peak table filtering. The workflow integrates four fully interactive modules for blank, ion-species, quality-control, and peak-based filtering, with synchronized processing of associated spectra files. The tool was evaluated across three independent datasets covering plant extracts, human cell lines, and bacterial interactions. Across these case studies, data filtering reduced feature redundancy and improved downstream interpretation in feature-based molecular networking, pathway-level functional analysis, and differential abundance testing, while retaining known analytes. MetaboCensoR was systematically benchmarked against existing tools, demonstrating comparable ion-species annotation coverage and a favorable overall balance of target recovery, adduct precision, and feature reduction. Together, these evaluations support MetaboCensoR as a robust approach for systematic peak table curation, enhancing interpretability and analytical value of untargeted metabolomics data.

bioinformatics↗

bioRxiv2026

Deciphering temporal antifungal dynamics of a rare actinomycete via integrated omics

Fungal phytopathogens pose a persistent threat to global crop production, and widespread use of chemical fungicides has driven resistance development and environmental concerns, necessitating sustainable alternatives. Actinomycetes produce diverse bioactive metabolites, yet natural product discovery has disproportionately focused on Streptomyces, leaving rare actinomycete taxa underexplored. Saccharomonospora xinjiangensis XJ-54 is a rare actinomycete exhibiting strong antifungal activity against Fusarium phytopathogens, including Fusarium oxysporum f. sp. cucumerinum (FORC), and harbors numerous biosynthetic gene clusters (BGCs) of unknown function. However, as in many rare actinomycetes, BGCs may be transcriptionally silent under standard laboratory conditions, and their expression dynamics remain poorly understood. To elucidate the molecular basis of antifungal activity in S. xinjiangensis XJ-54, we integrated genomic, transcriptomic, and metabolomic analyses. Cell-free supernatants inhibited FORC after 5 days of fermentation, with activity increasing by day 7. Time-resolved RNA sequencing demonstrated that all genomically-identified BGCs were transcriptionally active but exhibited distinct growth-phase-dependent expression patterns, with approximately half upregulated during exponential growth, and the remainder following transition to stationary phase. We observed temporal variations in transcriptional coupling between cluster-specific regulators and biosynthetic genes. LC-MS-based metabolomics showed growth-phase-dependent metabolite shifts, including stationary phase accumulation of secoiridoid-like monoterpenoids, N-acyl amines, and alkaloids (imidazoles, pyridines, indoles), correlating with the observed antifungal phenotype. Bioactivity-guided fractionation subsequently yielded an active fraction containing a predicted halogenated alkaloid that induced hyphal damage in FORC. These findings indicate that antifungal activity in S. xinjiangensis XJ-54 arises from temporally coordinated biosynthetic programs, providing a framework for optimizing growth conditions and prioritizing BGCs for functional characterization. ImportanceThe discovery of new antifungal compounds is critical for sustainable agriculture and medicine, yet most natural product research has focused on screening a narrow range of well-studied microorganisms. Rare actinomycetes represent an untapped reservoir of chemical diversity, but their biosynthetic potential is predominantly unknown. By integrating time-resolved transcriptomics with metabolomics, we show that the rare actinomycete Saccharomonospora xinjiangensis XJ-54 produces antifungal metabolites through temporally coordinated biosynthetic programs. Contrary to the prevailing assumption that the majority of biosynthetic gene clusters (BGCs) are silent, all BGCs in this strain were transcriptionally active under standard cultivation conditions, with expression patterns that were strongly growth-phase dependent. This work provides a roadmap for unlocking the biosynthetic potential of rare actinomycetes and accelerating the discovery of antifungal natural products that can be applied in agriculture and human health.

microbiology↗

bioRxiv2026

Biosynthetic diversity and antifungal potential of soil-derived Saccharomonospora strains

Soilborne fungal pathogens pose persistent challenges to sustainable agriculture, driving demand for biological alternatives to synthetic fungicides. While actinomycetes, particularly Streptomyces have yielded numerous antifungal compounds, less-explored genera, such as Saccharomonospora represent untapped sources of novel bioactive metabolites for plant protection. Our previous work identified Saccharomonospora as strongly associated with plant disease suppression in organically-amended soils and harbored numerous uncharacterized biosynthetic gene clusters (BGCs). Here, we investigated the biosynthetic capacity and antifungal potential of Saccharomonospora using comparative genomics, untargeted metabolomics, and in vitro bioassays. Cell-free supernatants from six strains (five soil-derived type strains and one novel isolate) were evaluated against three Fusarium phytopathogens. All strains inhibited at least one pathogen, with S. xinjiangensis and S. viridis R81 exhibiting the highest and broad-spectrum activity. Metabolomic profiling of the two most bioactive strains and one moderately active strain (S. cyanea) revealed that [~]40% of detected metabolites were shared across the three strains although their relative abundances varied. S. xinjiangensis and S. viridis R81 displayed higher abundances of shared metabolite classes than S. cyanea, including alkaloids, polyketides, and peptide derivatives. Comparative genomics across the genus revealed that most BGCs, particularly those encoding non-ribosomal peptides synthetases and polyketides synthases, were strain-specific and had low sequence similarity to characterized BGCs. In contrast, BGCs encoding, indole, ectoine, arylpolyene, and terpene were ubiquitous across the genus. Collectively, these findings demonstrate that Saccharomonospora produce antifungal metabolites and harbor diverse, uncharacterized BGCs, positioning this "less-explored" actinomycete genus as a promising source of bioactive compounds for managing soilborne fungal pathogens. ImportanceActinomycetes have historically been rich sources of antifungal metabolites for agriculture and pharmaceuticals, but discovery efforts have focused largely on Streptomyces, leaving other genera underexplored. This study demonstrates that Saccharomonospora, a rare actinomycete genus, produces antifungal metabolites active against major Fusarium pathogens and harbors largely uncharacterized biosynthetic gene clusters, indicating a reservoir of novel chemistry. These findings establish Saccharomonospora as a promising yet underutilized resource for discovering new antifungal agents, expanding the toolkit for sustainable plant disease management beyond traditional actinomycete sources.

microbiology↗

bioRxiv2022

Significant organic carbon acquisition by Prochlorococcus in the oceans

Marine phytoplankton are responsible for about half of the photosynthesis on Earth. Many are mixotrophs, combining photosynthesis with heterotrophic assimilation of organic carbon but the relative contribution of these two carbon sources is not well quantified. Here, single-cell measurements reveal that Prochlorococcus at the base of the photic zone in the Eastern Mediterranean Sea are obtaining only ~20% of carbon required for growth by photosynthesis. Consistently, laboratory-calibrated evaluations of Prochlorococcus photosynthesis indicate that carbon fixation is systematically too low to support published in situ growth rates in the deep photic layer of the Pacific Ocean. Furthermore, agent-based model simulations show that mixotrophic cells maintain realistic growth rates and populations 10s of meters deeper than obligate photo-autotrophs, deepening the nutricline and Deep Chlorophyll Maximum by ~20 m. Time-series of Prochlorococcus ecotype-abundance from the subtropical North Atlantic and North Pacific suggest that up to 30% of the Prochlorococcus cells live where light intensity is not enough to sustain obligate photo-autotrophic populations during warm, stratified periods. Together, these data and models suggest that mixotrophy underpins the ecological success of a large fraction of the global Prochlorococcus population and its collective genetic diversity.

microbiology↗

bioRxiv2019

The Molecular and Microbial Microenvironments in Chronically Diseased Lungs

To visualize the personalized distributions of pathogens, chemical environments including microbial metabolites, pharmaceuticals, and their metabolic products within and between human lungs afflicted with cystic fibrosis, we generated 3D microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments are variable between patients and within the lungs of each patient. Although the patients microbial ecosystems were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in lungs of the same individual sometimes exceeded inter-individual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate a complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.\n\nImportanceMicrobial infections are now recognized to be polymicrobial and personalized in nature. A comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remains limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we describe how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment, or vice versa. We highlight that three-dimensional organ mapping are hypothesis building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs.

microbiology↗

bioRxiv2019

Prochlorococcus rely on microbial interactions rather than on chlorotic resting stages to survive long-term stress

Many microorganisms produce resting cells with very low metabolic activity that allow them to survive phases of prolonged nutrient or energy stress. In cyanobacteria and some eukaryotic phytoplankton, the production of resting stages is accompanied by a loss of photosynthetic pigments, a process termed chlorosis. Here, we show that a chlorosis-like process occurs under multiple stress conditions in axenic laboratory cultures of Prochlorococcus, the dominant phytoplankton linage in large regions of the oligotrophic ocean and a global key player in ocean biogeochemical cycles. In Prochlorococcus strain MIT9313, chlorotic cells show reduced metabolic activity, measured as C and N uptake by NanoSIMS. However, unlike many other cyanobacteria, chlorotic Prochlorococcus cells are not viable and do not re-grow under axenic conditions when transferred to new media. Nevertheless, co-cultures with a heterotrophic bacterium, Alteromonas macleodii HOT1A3, allowed Prochlorococcus to survive nutrient starvation for months. We propose that reliance on co-occurring heterotrophic bacteria, rather than the ability to survive extended starvation as resting cells, underlies the ecological success of Prochlorococcus. ImportanceThe ability of microorganisms to withstand long periods of nutrient starvation is key to their survival and success under highly fluctuating conditions as is common in nature. Therefore, one would expect this trait to be prevalent among organisms in the nutrient-poor open ocean. Here, we show that this is not the case for Prochlorococcus, a globally abundant and ecologically impactful marine cyanobacterium. Instead, Prochlorococcus rely on co-occurring heterotrophic bacteria to survive extended phases of nutrient and light starvation. Our results highlight the power of microbial interactions to drive major biogeochemical cycles in the ocean and elsewhere with consequences at the global scale.

microbiology↗