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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Mevalonate 5-diphosphate mediates ATP binding to the mevalonate diphosphate decarboxylase from the bacterial pathogen Enterococcus faecalis

The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block for polyisoprenoid synthesis, and is a crucial pathway for growth of the human bacterial pathogen Enterococcus faecalis. The final enzyme in this pathway, mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been suggested as a therapeutic target for the treatment of drug-resistant bacterial infections. Here, we report functional and structural studies on the mevalonate diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure in complex with ATP (MDDEF–ATP) revealed that the phosphate-binding loop (amino acids 97–105) is not involved in ATP binding and that the phosphate tail of ATP in this structure is in an outward-facing position pointing away from the active site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP into a catalytically favorable position. Enzymology experiments show that the MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first substrate, consistent with the isothermal titration calorimetry (ITC) experiments. On the basis of ITC results, we propose that this initial prerequisite binding of MVAPP enhances ATP binding. In summary, our findings reveal a substrate-induced substrate-binding event that occurs during the MDDEF-catalyzed reaction. The disengagement of the phosphate-binding loop concomitant with the alternative ATP-binding configuration may provide the structural basis for antimicrobial design against these pathogenic enterococci.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

CRISPR-GRIT: Guide RNAs with Integrated Repair Templates Enable Precise Multiplexed Genome Editing in the Diploid Fungal Pathogen Candida albicans

Candida albicans, an opportunistic fungal pathogen, causes severe infections in immunocompromised individuals. Limited classes and overuse of current antifungals have led to the rapid emergence of antifungal resistance. Thus, there is an urgent need to understand fungal pathogen genetics to develop new antifungal strategies. Genetic manipulation of C. albicans is encumbered by its diploid chromosomes requiring editing both alleles to elucidate gene function. Although the recent development of CRISPR-Cas systems has facilitated genome editing in C. albicans, large-scale and multiplexed functional genomic studies are still hindered by the necessity of cotransforming repair templates for homozygous knockouts. Here, we present CRISPR-GRIT (Guide RNAs with Integrated Repair Templates), a repair template-integrated guide RNA design for expedited gene knockouts and multiplexed gene editing in C. albicans. Here, we envision that this method can be used for high-throughput library screens and identification of synthetic lethal pairs in both C. albicans and other diploid organisms with strong homologous recombination machinery.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Hypothesis on the dust-borne atmospheric transport of Coccidioides , causative fungal pathogen for coccidioidomycosis (Valley fever)

For many decades, the fungal pathogen (Coccidioides spp.) that causes coccidioidomycosis (Valley fever) has been associated with dust exposure. However, the mechanism of atmospheric transport of arthroconidia has yet to be defined. As such, it is unclear whether the association between dust exposure and Coccidioides is coincidental or not: do soil-disturbing events simultaneously cause both free-floating Coccidioides conidia and dust particles (i.e., particulate matter) to become entrained in the atmosphere, or is Coccidioides attached to dust particles and they are jointly suspended? In this short article, we propose the dust-borne atmospheric transport hypothesis: Coccidioides conidia are transported in the atmosphere attached to dust particles, which protect the fungi from harsh environmental conditions like desiccation and UV exposure, allowing them to travel far while remaining viable in comparison to free-floating aerial transport. If true, the dust-borne atmospheric transport hypothesis provides a means for mechanistically modeling the transport and exposure risk of Coccidioides via atmospheric dispersion modeling and suggests health implications from simultaneous exposure to dust and a fungal pathogen.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Structure of the virulence-associated protein VapD from the intracellular pathogen Rhodococcus equi

VapD is one of a set of highly homologous virulence-associated proteins from the multi-host pathogen Rhodococcus equi. The crystal structure reveals an eight-stranded β-barrel with a novel fold and a glycine rich ‘bald’ surface. Rhodococcus equi is a multi-host pathogen that infects a range of animals as well as immune-compromised humans. Equine and porcine isolates harbour a virulence plasmid encoding a homologous family of virulence-associated proteins associated with the capacity of R. equi to divert the normal processes of endosomal maturation, enabling bacterial survival and proliferation in alveolar macrophages. To provide a basis for probing the function of the Vap proteins in virulence, the crystal structure of VapD was determined. VapD is a monomer as determined by multi-angle laser light scattering. The structure reveals an elliptical, compact eight-stranded β-barrel with a novel strand topology and pseudo-twofold symmetry, suggesting evolution from an ancestral dimer. Surface-associated octyl-β-d-glucoside molecules may provide clues to function. Circular-dichroism spectroscopic analysis suggests that the β-barrel structure is preceded by a natively disordered region at the N-terminus. Sequence comparisons indicate that the core folds of the other plasmid-encoded virulence-associated proteins from R. equi strains are similar to that of VapD. It is further shown that sequences encoding putative R. equi Vap-like proteins occur in diverse bacterial species. Finally, the functional implications of the structure are discussed in the light of the unique structural features of VapD and its partial structural similarity to other β-barrel proteins.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2018

A Review of Water Quality Responses to Air Temperature and Precipitation Changes 2: Nutrients, Algal Blooms, Sediment, Pathogens

Abstract In this paper we review the published, scientific literature addressing the response of nutrients, sediment, pathogens, and cyanobacterial blooms to historical and potential future changes in air temperature and precipitation. The goal is to document how different attributes of water quality are sensitive to these drivers, to characterize future risk, to inform management responses, and to identify research needs to fill gaps in our understanding. Results suggest that anticipated future changes present a risk of water quality and ecosystem degradation in many United States locations. Understanding responses is, however, complicated by inherent high spatial and temporal variability, interactions with land use and water management, and dependence on uncertain changes in hydrology in response to future climate. Effects on pollutant loading in different watershed settings generally correlate with projected changes in precipitation and runoff. In all regions, increased heavy precipitation events are likely to drive more episodic pollutant loading to water bodies. The risk of algal blooms could increase due to an expanded seasonal window of warm water temperatures and the potential for episodic increases in nutrient loading. Increased air and water temperatures are also likely to affect the survival of waterborne pathogens. Responding to these challenges requires understanding of vulnerabilities, and management strategies to reduce risk.

Coffey, Rory↗
DOE OSTI2019

An avian influenza virus A(H7N9) reassortant that recently emerged in the United States with low pathogenic phenotype does not efficiently infect swine

In 2017, outbreaks of low and highly pathogenic avian H7N9 viruses were reported in four States in the United States. In total, over 270 000 birds died or were culled, causing significant economic loss. The potential for avian‐to‐swine transmission of the U.S. avian H7N9 was unknown. In an experimental challenge in swine using a representative low pathogenic H7N9 (A/chicken/Tennessee/17‐007431‐3/2017; LPAI TN /17) isolated from these events, no infectious virus in the upper and minimal virus in the lower respiratory tract was detected, nor was lung pathology or evidence of transmission in pigs observed, indicating that the virus cannot efficiently infect swine.

H7N9↗
DOE OSTI2019

Selection and characterization of ssDNA aptamers specifically recognizing pathogenic Vibrio alginolyticus

Abstract Vibrio alginolyticus ( V. alginolyticus ) is a major opportunistic pathogen to both marine animals and humans, which has also caused heavy economic losses to mariculture. The aim of this study was to develop highly specific aptamers for V. alginolyticus . Single‐stranded DNA (ssDNA) aptamers with high binding affinity to viable V. alginolyticus were generated by Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and identified by flow cytometric analysis in this study. The selected aptamers showed high specificity for V. alginolyticus and low apparent binding for other bacteria. The aptamers formed distinct stem‐loop structures, which could form the basis of aptamers’ specific binding to the target V. alginolyticus . Aptamer VA2 and VA8 showed particularly high binding affinity constant (K d ) of 14.31 ± 4.26 and 90.00 ± 13.51 nM, respectively. The aptamers produced no cytotoxic effects in vitro and in vivo. ssDNA aptamers were successfully selected against the viable bacteria pathogen V. alginolyticus by SELEX. The aptamers selected in this study could be not only applied as specific chemical molecular probes for studying V. alginolyticus pathogenesis to Trachinotus ovatus , but also developing rapid convenient diagnosis assay for V. alginolyticus infection, even when applied to the complex sample matrix, such as food and environment samples.

Yu, Qing↗
DOE OSTI2022

Phylogenetic conservatism of mycoparasitism and its contribution to pathogen antagonism

Abstract Closely related species are expected to have similar functional traits due to shared ancestry and phylogenetic inertia. However, few tests of this hypothesis are available for plant‐associated fungal symbionts. Fungal leaf endophytes occur in all land plants and can protect their host plant from disease by a variety of mechanisms, including by parasitizing pathogens (e.g., mycoparasitism). Here, we tested whether phylogenetic relatedness among species of Cladosporium , a widespread genus that includes mycoparasitic species, predicts the effect of this endophyte on the severity of leaf rust disease. First, we used congruence among different marker sequences (i.e., genealogical concordance phylogenetic species recognition criterion) to delimit species of Cladosporium . Next, in a controlled experiment, we quantified both mycoparasitism and disease modification for the selected Cladosporium species. We identified 17 species of Cladosporium ; all the species reduced rust disease severity in our experiment. Cladosporium phylogeny was a significant predictor of mycoparasitism. However, we did not observe a phylogenetic effect on disease severity overall, indicating that other mechanism/s operating independently of shared ancestry also contributed to endophyte effects on disease severity. Indeed, a second experiment showed that Cladosporium endophyte exudates (no live organism) from divergent species groups equally reduced disease severity. Our results reveal that multiple mechanisms contribute to the protective effects of an endophyte against a plant pathogen, but not all traits underlying these mechanisms are phylogenetically conserved.

Barge, Edward G.↗
DOE OSTI2018

Know your enemy, embrace your friend: using omics to understand how plants respond differently to pathogenic and mutualistic microorganisms

Summary Microorganisms, or ‘microbes’, have formed intimate associations with plants throughout the length of their evolutionary history. In extant plant systems microbes still remain an integral part of the ecological landscape, impacting plant health, productivity and long‐term fitness. Therefore, to properly understand the genetic wiring of plants, we must first determine what perception systems plants have evolved to parse beneficial from commensal from pathogenic microbes. In this review, we consider some of the most recent advances in how plants respond at the molecular level to different microbial lifestyles. Further, we cover some of the means by which microbes are able to manipulate plant signaling pathways through altered destructiveness and nutrient sinks, as well as the use of effector proteins and micro‐ RNA s (mi RNA s). We conclude by highlighting some of the major questions still to be answered in the field of plant‐microbe research, and suggest some of the key areas that are in greatest need of further research investment. The results of these proposed studies will have impacts in a wide range of plant research disciplines and will, ultimately, translate into stronger agronomic crops and forestry stock, with immune perception and response systems bred to foster beneficial microbial symbioses while repudiating pathogenic symbioses.

Plett, Jonathan M.↗
DOE OSTI2017

The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion

Robust innate immune detection of rapidly evolving pathogens is critical for host defense. Nucleotide-binding domain leucine-rich repeat (NLR) proteins function as cytosolic innate immune sensors in plants and animals. However, the structural basis for ligand-induced NLR activation has so far remained unknown. NAIP5 (NLR family, apoptosis inhibitory protein 5) binds the bacterial protein flagellin and assembles with NLRC4 to form a multiprotein complex called an inflammasome. Here we report the cryo–electron microscopy structure of the assembled ~1.4-megadalton flagellin-NAIP5-NLRC4 inflammasome, revealing how a ligand activates an NLR. Six distinct NAIP5 domains contact multiple conserved regions of flagellin, prying NAIP5 into an open and active conformation. We show that innate immune recognition of multiple ligand surfaces is a generalizable strategy that limits pathogen evolution and immune escape.

Tenthorey, Jeannette L.↗
DOE OSTI2019

A layered defense against plant pathogens

Diseases affecting crops take a toll on agricultural yields worldwide. Strategies to eradicate or mitigate these pathogens include breeding resistant genotypes, crop rotation, and chemical or biological treatments. A phenomenon called “suppressive soils” has attracted considerable interest because such soils can reduce disease incidence despite pathogen presence, a susceptible host, and favorable conditions for infection. If the secrets of suppressive soils could be unlocked, it might be possible to confer suppressiveness to other soils without the risks and losses associated with repeated cropping on disease-affected fields. Suppressive soils have long been suspected to be mediated by microbiota, particularly because suppressiveness is lost upon sterilization and can be transferred from one soil to another through mixing. Finally, on page 606 of this issue, Carrión et al. (1) demonstrate that they can confer disease suppressiveness when specific bacteria are added as a consortium to a conducive soil.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A phage tail–like bacteriocin suppresses competitors in metapopulations of pathogenic bacteria

Bacteria can repurpose their own bacteriophage viruses (phage) to kill competing bacteria. Phage-derived elements are frequently strain specific in their killing activity, although there is limited evidence that this specificity drives bacterial population dynamics. Here, in this study, we identified intact phage and their derived elements in a metapopulation of wild plant–associated Pseudomonas genomes. We discovered that the most abundant viral cluster encodes a phage remnant resembling a phage tail called a tailocin, which bacteria have co-opted to kill bacterial competitors. Each pathogenic Pseudomonas strain carries one of a few distinct tailocin variants that target the variable polysaccharides in the outer membrane of co-occurring pathogenic Pseudomonas strains. Analysis of herbarium samples from the past 170 years revealed that the same tailocin and bacterial receptor variants have persisted in Pseudomonas populations. These results suggest that tailocin genetic diversity can be mined to develop targeted “tailocin cocktails” for microbial control.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Field application of pathogen detection technologies

Over the last 10 years there has been a significant increase in commercial products designed for field-based detection of microbial pathogens. This is due, in part, to the anthrax attacks in the United States in 2001, and the need for first responders to quickly identify the composition of suspected white powders and other potential biothreats. Demand for rapid detection is also driven by the need to ensure safe food, water, and environmental systems. From a technology perspective, rapid identification methods have largely capitalized on PCR and other molecular recognition techniques that can be deployed as robust field instrumentation. Examples of the relevant needs include the ability to: 1) declare a water distribution system free of microbial pathogens after a pipe/main break repair; 2) assess risks of contamination such as when produce production and processing plants are located near concentrated animal feeing operations; 3) evaluate the safety of ready-to-eat products; 4) determine the extent of potential serious disease outbreaks in remote and/or disaster stricken areas where access to clinical laboratories is not an immediate option; and 5) quickly assess credible biological terrorism events. Many of the principles underlying rapid detection methods are derived from methods for environmental microbiology, but there is a dearth of literature describing and evaluating field-based detection systems. Thus, the aims of this chapter are to: 1) summarize the different kinds of commercially available sampling kits and field-based biological detectors; 2) highlight some of the continued challenges of sample preparation to stimulate new research towards minimizing the impact of inhibitors on PCR-based detection systems; 3) describe our general rationale and statistically-based approach for instrument evaluation; 4) provide statistical and spatial guidelines for developing valid sampling plans; and 5) summarize some current needs and emerging technologies. This information is presented both to highlight the state of the field, and to also highlight major questions that students may wish to consider investigating further. Where possible we will cite studies that have been conducted and published either in traditional peer-reviewed or other literature (e.g., AOAC International Methods).

Straub, Tim M.↗
DOE OSTI2019

Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae

Neisseria gonorrhoeae responds to host-derived antimicrobials by inducing the expression of the mtrCDE -encoded multidrug efflux pump, which expels microbicides, such as bile salts, fatty acids, and multiple extrinsically administered drugs, from the cell. In the absence of these cytotoxins, the TetR family member MtrR represses the mtrCDE genes. Although antimicrobial-dependent derepression of mtrCDE is clear, the physiological inducers of MtrR are unknown. Here, we report the crystal structure of an induced form of MtrR. In the binding pocket of MtrR, we observed electron density that we hypothesized was N -cyclohexyl-3-aminopropanesulfonic acid (CAPS), a component of the crystallization reagent. Using the MtrR-CAPS structure as an inducer-bound template, we hypothesized that bile salts, which bear significant chemical resemblance to CAPS, are physiologically relevant inducers. Indeed, characterization of MtrR-chenodeoxycholate and MtrR-taurodeoxycholate interactions, both in vitro and in vivo , revealed that these bile salts, but not glyocholate or taurocholate, bind MtrR tightly and can act as bona fide inducers. Furthermore, two residues, W136 and R176, were shown to be important in binding chenodeoxycholate but not taurodeoxycholate, suggesting different binding modes of the bile salts. These data provide insight into a crucial mechanism utilized by the pathogen to overcome innate human defenses. IMPORTANCE Neisseria gonorrhoeae causes a significant disease burden worldwide, and a meteoric rise in its multidrug resistance has reduced the efficacy of antibiotics previously or currently approved for therapy of gonorrheal infections. The multidrug efflux pump MtrCDE transports multiple drugs and host-derived antimicrobials from the bacterial cell and confers survival advantage on the pathogen within the host. Transcription of the pump is repressed by MtrR but relieved by the cytosolic influx of antimicrobials. Here, we describe the structure of induced MtrR and use this structure to identify bile salts as physiological inducers of MtrR. These findings provide a mechanistic basis for antimicrobial sensing and gonococcal protection by MtrR through the derepression of mtrCDE expression after exposure to intrinsic and clinically applied antimicrobials.

Neisseria gonorrhoeaebile↗
DOE OSTI2018

Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge

ABSTRACT Broadly cross-reactive antibodies (Abs) that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes, including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (MAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the MAbs bound HAs from multiple strains of group 1 viruses, and one MAb, 05-2G02, bound to both group 1 and group 2 influenza A virus HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two MAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One MAb, 70-1F02, cocrystallized with H5 HA and showed heavy-chain-only interactions similar to those seen with the previously described CR6261 anti-stalk antibody. Finally, we show that antibodies that compete with these MAbs are prevalent in serum from an individual recently infected with the A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections by zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved “stalk” domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.

Nachbagauer, Raffael (ORCID:0000000155685420)↗
DOE OSTI2016

Structures of Pathogenic Fungal FKBP12s Reveal Possible Self-Catalysis Function

Invasive fungal infections remain difficult to treat and require novel targeting strategies. The 12-kDa FK506-binding protein (FKBP12) is a ubiquitously expressed peptidyl-prolyl isomerase with considerable homology between fungal pathogens and is thus a prime candidate for future targeting efforts to generate a panfungal strategy. Despite decades of research on FKBPs, their substrates and mechanisms of action remain unclear. Here we describe structural, biochemical, and in vivo analyses of FKBP12s from the pathogenic fungi Candida albicans, Candida glabrata, and Aspergillus fumigatus. Strikingly, multiple apo A. fumigatus and C. albicans FKBP12 crystal structures revealed a symmetric, intermolecular interaction involving the deep insertion of an active-site loop proline into the active-site pocket of an adjacent subunit. Such interactions have not been observed in previous FKBP structures. This finding indicates the possibility that this is a self-substrate interaction unique to the A. fumigatus and C. albicans fungal proteins that contain this central proline. Structures obtained with the proline in the cis and trans states provide more data in support of self-catalysis. Moreover, cysteine cross-linking experiments captured the interacting dimer, supporting the idea that it forms in solution. Finally, genetic studies exploring the impact of mutations altering the central proline and an adjacent residue provide evidence that any dimeric state formed in vivo, where FKBP12 concentrations are low, is transient. Taken together, these findings suggest a unique mechanism of self-substrate regulation by fungal FKBP12s, lending further novel understanding of this protein for future drug-targeting efforts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Structural and In Vivo Studies on Trehalose-6-Phosphate Synthase from Pathogenic Fungi Provide Insights into Its Catalytic Mechanism, Biological Necessity, and Potential for Novel Antifungal Drug Design

ABSTRACT The disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. Trehalose-6-phosphate synthase (Tps1) catalyzes the first step of trehalose biosynthesis in fungi. Here, we report the first structures of eukaryotic Tps1s in complex with substrates or substrate analogues. The overall structures of Tps1 from Candida albicans and Aspergillus fumigatus are essentially identical and reveal N- and C-terminal Rossmann fold domains that form the glucose-6-phosphate and UDP-glucose substrate binding sites, respectively. These Tps1 structures with substrates or substrate analogues reveal key residues involved in recognition and catalysis. Disruption of these key residues severely impaired Tps1 enzymatic activity. Subsequent cellular analyses also highlight the enzymatic function of Tps1 in thermotolerance, yeast-hypha transition, and biofilm development. These results suggest that Tps1 enzymatic functionality is essential for the fungal stress response and virulence. Furthermore, structures of Tps1 in complex with the nonhydrolyzable inhibitor, validoxylamine A, visualize the transition state and support an internal return-like catalytic mechanism that is generalizable to other GT-B-fold retaining glycosyltransferases. Collectively, our results depict key Tps1-substrate interactions, unveil the enzymatic mechanism of these fungal proteins, and pave the way for high-throughput inhibitor screening buttressed and guided by the current structures and those of high-affinity ligand-Tps1 complexes. IMPORTANCE Invasive fungal diseases have emerged as major threats, resulting in more than 1.5 million deaths annually worldwide. This epidemic has been further complicated by increasing resistance to all major classes of antifungal drugs in the clinic. Trehalose biosynthesis is essential for the fungal stress response and virulence. Critically, this biosynthetic pathway is absent in mammals, and thus, the two enzymes that carry out trehalose biosynthesis, namely, trehalose-6-phosphate synthase (Tps1) and trehalose-6-phosphate phosphatase (Tps2), are prominent targets for antifungal intervention. Here, we report the first eukaryotic Tps1 structures from the pathogenic fungi Candida albicans and Aspergillus fumigatus in complex with substrates, substrate analogues, and inhibitors. These structures reveal key protein-substrate interactions, providing atomic-level scaffolds for structure-guided drug design of novel antifungals that target Tps1.

Miao, Yi↗