Biology subjects

Sengupta, P.

Publications and source records attributed to Sengupta, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Neuron-intrinsic and glial pathways regulate sensory cilia regeneration in adult C. elegans

Primary cilia are microtubule-based organelles that mediate cellular responses to environmental cues. Although cilia disassemble and reassemble upon cell cycle entry and exit, respectively, in dividing cells, it remains unclear whether postmitotic cells such as neurons can regenerate these structures in vivo following injury to restore function, and whether this process recapitulates developmental ciliogenesis. Here we show that a subset of sensory neuron cilia in adult C. elegans regrows following conditional truncation and restores neuronal functions. This regeneration is regulated by both cell-intrinsic and extrinsic mechanisms that are in part distinct from those employed during embryonic ciliogenesis. We find that the conserved ciliogenic DAF-19 RFX transcription factor is dispensable for cilia maintenance in the adult but is required for regeneration, in part via transcriptional upregulation of a subset of ciliary intraflagellar transport (IFT) genes. We further identify the DLK-1 dual leucine-zipper kinase and the CEBP-1 C/EBP transcription factor, previously implicated in axon regeneration, as necessary for efficient cilia regrowth but not for developmental ciliogenesis. We show that cebp-1 expression is induced during cilia truncation and regrowth and that this induction is also DAF-19-dependent. Finally, we show that cilia truncation and regeneration dynamics vary in a neuron type-specific manner and are modulated by signals from surrounding glia. Our results establish that the cilia of mature neurons can regenerate and recover functions in vivo and identify conserved pathways that regulate this process in adult animals.

cell biology↗

bioRxiv2026

A repressive regulatory cascade shapes temporal patterning of activity-regulated gene expression in a defined sensory neuron type

Long-term neuronal plasticity is driven by activity-regulated gene (ARG) expression programs that encode stimulus features in a neuron type-specific manner 1-6. ARG programs are typically characterized by rapid induction of immediate early genes (IEGs) without requiring new protein synthesis, followed by expression of secondary response genes regulated by IEG-encoded transcription factors 2,5,7-14. However, the molecular mechanisms that pattern these programs in specific neuron types in vivo in response to physiological stimuli are not fully described. We previously showed that temperature regulates an ARG program in the C. elegans AFD thermosensory neuron pair to drive behavioral plasticity 3,15,16. By profiling AFD following temperature upshifts of varying duration, here we show that ARGs in this neuron exhibit distinct temporal trajectories. Notably, rapidly induced genes do not include known IEGs but are enriched for molecules implicated in signal transduction and navigation. Both rapid and delayed ARG expression require the CMK-1 CaMKI kinase and CRH-1 CREB transcription factor, with CRH-1 acting at both early and late stages. We further define a temporal regulatory cascade in which CREB-dependent rapid induction of the RCAN-1 calcineurin regulator acts in parallel with the MEF-2 transcription factor to repress premature expression of a delayed ARG. Subsequent downregulation of RCAN-1 likely enables CRH-1-dependent ARG expression at later stages. Our results demonstrate that in addition to classical gene-activating transcriptional cascades, ARG-controlled repressive mechanisms also operate to precisely shape the temporal dynamics of an ARG cascade in a sensory neuron type in vivo, and suggest that distinct cell type-specific regulatory pathways operate to drive ARG expression programs across neuron types.

neuroscience↗

bioRxiv2026

Activity induced GEM-4/Copine expression inhibits gap junctions and promotes thermosensory plasticity

Activity induced gene expression promotes behavioral plasticity (including several forms of learning and memory) by altering synaptic connectivity and neuron excitability. While several transcriptional targets modify synapses, little is known about targets regulating excitability. Here, we identify a single MEF-2 and CRH-1/CREB transcriptional target, gem-4/Copine, whose expression increases the excitability of C. elegans body muscles. In muscles, gem-4 expression is repressed by MEF-2 and is induced by CRH-1. GEM-4 expression in muscles decreases the number of gap junctions, thereby increasing membrane resistance and excitability. These results identify activity induced copine expression as a mechanism to control gap junction coupling and excitability.

neuroscience↗

bioRxiv2026

Stereotypical interciliary contacts in a C. elegans sense organ

Physical interactions among cells and their processes are critical for intercellular communication and the generation of ordered tissue patterns. Primary cilia projecting from the cell surface have recently been shown to form contacts with the processes of diverse cell types, as well as with other cilia, in the brain and other organs. Whether these ciliary contacts are established in an instructive manner or are formed passively due to physical proximity is unclear. Ultrastructural analyses previously showed that the cilia of a subset of sensory neurons in the head amphid organs of C. elegans exhibit interciliary contacts within a glia-defined channel. Here we show that these ciliary contact patterns are stereotyped and can be established in the absence of neighboring cilia, indicating that these associations may not simply reflect relative positioning within the amphid channel. We show that mutations in genes implicated in ciliary protein trafficking, ciliary membrane phospholipid composition, and cilia-cell interactions disrupt cilia structure and/or interciliary contacts, and that in a subset of mutants, cilia with altered morphologies can nevertheless establish correct contacts. Together, our findings suggest that cilia-cilia interactions within a sense organ are established via instructive mechanisms, and raise the possibility that cellular functions may be modulated by cilia-mediated intercellular communication. SummaryThis work investigates how primary cilia, structures that detect and transmit signals, form contacts with one another in a head sensory organ of the nematode Caenorhabditis elegans. The authors found that these contacts follow consistent patterns and can form even when neighboring cilia are absent, suggesting they are actively established rather than occurring due to physical proximity. The authors identified mutations in genes that regulate cilia protein content, membrane composition, and cellular adhesion that disrupt cilia structure or contacts. These findings suggest that cilia-cilia interactions are regulated, raising the possibility that they play important roles in cell communication.

cell biology↗

bioRxiv2026

A stereotyped glial attachment determines the morphology and function of neuronal cilia

Primary cilia are signaling hubs that influence nearly every aspect of cell physiology. Neuronal primary cilia were recently discovered to interact with glia in the mammalian brain, but how cilia-glia attachments form and what roles they play remain unknown. Here, we find that two C. elegans sensory neurons (URX and BAG) use their primary cilia to attach to a specific glial partner (ILsoL). Through a genetic screen, we find that cilia-glia attachment requires BUG-1, a secreted protein with conserved cell adhesion domains that localizes to the cilia-glia attachment site. In the absence of BUG-1, neuronal cilia are present but fail to attach to the glial cell. We find that loss of cilia-glia attachment alters cilia morphology and disrupts stimulus-evoked calcium dynamics in cilia. We propose that primary cilia not only act as antennae for long-range cell communication, but also form close-range cell attachments that modulate cell signaling.

developmental biology↗

bioRxiv2025

Plasmidome, resistome, and virulence-associated genes characterization of Acinetobacter johnsonii in NASA cleanrooms and a clinical setting.

Evidence shows persistence of non-spore-forming Acinetobacter johnsonii in high-stakes controlled and nutrient-limited environments. This study aims to explore the mechanisms underpinning such adaptability through a comprehensive genomic analysis of 22 isolates of A. johnsonii from NASAs Payload Hazardous Servicing Facility (PHSF) and one carbapenem-resistant strain (E154408A) from patient colonization in Ireland. Core-genome phylogeny revealed clustering of PHSF-originating isolates in a monophyletic clade divergent from the main species lineage. Species-wide virulence-associated genes and metabolic profiling indicated the unique presence in PHSF-originating isolates of two complete efflux pumps and of a conserved allantoin racemase, suggesting adaptability for multiple environmental stresses. Observed ubiquity of blaOXA in investigated genomes (n=112) and phenotypically-validated multidrug-resistant profile of E154408A strain highlight A. johnsoniis potential as antimicrobial resistance (AMR) reservoir. Plasmidome analysis suggested gain/loss events across the monophyletic population and potential AMR acquisition pathways. Genome-to-metagenome mapping identified genomic signatures of A. johnsonii in PHSF >10 years post initial isolation. ImportanceAcinetobacter johnsonii is increasingly recognized as an emerging human pathogen, with growing evidence of its ability to persist in controlled, high-stakes environments, posing risks as both persisting environmental contaminant and antimicrobial resistance (AMR) reservoir. Yet, gaps remain in our understanding of its AMR profile and the mechanisms that enable its enhanced environmental adaptability. This knowledge is necessary in contexts where biological cleanliness is a priority such as clinical settings and spacecraft assembly facilities cleanrooms, where contamination of hardware with terrestrial microorganisms is concerning. In this study, we aim to address some of key knowledge gaps by providing genomic insights into a rare multi-drug resistant clinical isolate and 22 NASA cleanroom isolates that persisted for over a decade in extremely clean conditions. Our findings will help evaluate the contamination risk of A. johnsonii in high-stakes environments and ultimately strengthen our ability to manage this microbial contaminant across terrestrial and extraterrestrial settings. HighlightsO_LICleanrooms-derived A. johnsonii genomes show favorable traits for increased adaptability C_LIO_LIGenomic signatures of A. johnsonii persisted in the cleanrooms for >10 years C_LIO_LIblaOXA is ubiquitously found in the genome of all A. johnsonii C_LIO_LIE154408A is the first patient colonization by carbapenem-resistant A. johnsonii in Europe C_LI

genomics↗

bioRxiv2025

A genetic screen to identify deubiquitinases as regulators of IRF7

Virus infection rapidly induces the production and secretion of interferons (IFNs), amplifying antiviral responses in infected and neighboring uninfected cells. IFN regulatory factor 7 (IRF7), the master transcription factor, is pivotal in IFN induction, particularly in myeloid cells. Ubiquitination of IRF7 is essential for its transcriptional activation; however, the underlying molecular mechanisms remain poorly understood. We hypothesized that deubiquitinases (DUBs) act as endogenous regulators of IRF7 activity and conducted a genetic screen using a human DUB-targeted siRNA library. This screen identified USP2 as a positive regulator and OTUD5 as a negative regulator of IRF7 activity. OTUD5, an inducible DUB, physically interacted with IRF7 and inhibited its K63-linked ubiquitination, thereby suppressing IRF7 activation. Conversely, USP2 promoted IRF7 activity by binding to IRF7 and removing K27-linked ubiquitin chains, which we found to be inhibitory. Specifically, K27-linked ubiquitination impeded phosphorylation of IRF7, a critical step for its activation. Collectively, our genetic screen and mechanistic studies uncovered USP2 and OTUD5 as novel modulators of IRF7 function, providing new insights into the regulation of antiviral immunity.

immunology↗

bioRxiv2025

Experience-dependent reconfiguration of receptors at a sensory compartment regulates neuronal plasticity

Neurons continuously adjust their properties as a function of experience. Precise modulation of neuronal responses is achieved by multiple cellular mechanisms that operate over a range of timescales. Primary sensory neurons rapidly adapt their sensitivities via posttranslational mechanisms including regulated trafficking of sensory molecules1-4 but also alter their transcriptional profiles on longer timescales to adapt to persistent sensory stimuli5-8. How diverse transcriptional and posttranscriptional pathways are coordinated in individual sensory neurons to accurately adjust their functions and drive behavioral plasticity is unclear. Here we show that temperature experience modulates both transcription and trafficking of thermoreceptors on different timescales in the C. elegans AFD thermosensory neurons to regulate response plasticity. Expression of the PY motif-containing adaptor protein (PYT-1) as well as the GCY-18 warm temperature-responsive guanylyl cyclase thermoreceptor9 is transcriptionally upregulated in AFD upon a temperature upshift5,10. We find that as GCY-18 begins to accumulate at the AFD sensory endings, the GCY-23 cooler temperature-responsive thermoreceptor9 exhibits altered subcellular localization and increased retrograde trafficking, thereby increasing the functional GCY-18 to GCY-23 ratio in the AFD sensory compartment. Altered GCY-23 localization and trafficking requires PYT-1-dependent endocytosis, and we show that PYT-1-mediated modulation of the GCY-18 to GCY-23 protein ratio at the AFD sensory endings is necessary to shift the AFD response threshold towards warmer values following the temperature upshift. Our results describe a mechanism by which transcriptional and posttranscriptional mechanisms are temporally coordinated across sensory receptors to fine tune experience-dependent plasticity in the response of a single sensory neuron type.

neuroscience↗

bioRxiv2025

A lateralized sensory signaling pathway mediates context-dependent olfactory plasticity in C. elegans

Lateralization of neuronal functions plays a critical role in regulating behavioral flexibility, but the underlying molecular mechanisms are challenging to establish at a single-neuron level. We previously showed that attraction of C. elegans to a medium-chain alcohol switches to avoidance in a uniform background of a second attractive odorant. This context-dependent behavioral plasticity is mediated by symmetric inversion of the odor-evoked response sign in the bilateral AWC olfactory neurons. Here we show that this symmetric response plasticity is driven by asymmetric molecular mechanisms in the AWC neuron pair. Mutations in the gcy-12 receptor guanylyl cyclase abolish odor response plasticity only in AWCOFF; the opposing odor-evoked response signs in AWCOFF and AWCON in gcy-12 mutants results in these animals being behaviorally indifferent to this chemical. We find that gcy-12 is expressed, and required, in both AWC neurons to regulate odor response plasticity only in AWCOFF. We further show that disruption of AWC fate lateralization results in loss of asymmetry in the response plasticity in gcy-12 mutants. Our results indicate that symmetric neuronal response plasticity can arise from asymmetry in underlying molecular mechanisms, and suggest that lateralization of signaling pathways in defined conditions may enhance neuronal and behavioral flexibility.

neuroscience↗

bioRxiv2025

An enteric neuron-expressed variant ionotropic receptor detects ingested salts to regulate salt stress resistance

The detection of internal chemicals by interoceptive chemosensory pathways is critical for regulating metabolism and physiology. The molecular identities of interoceptors, and the functional consequences of chemosensation by specific interoceptive neurons remain to be fully described. The C. elegans pharyngeal neuronal network is anatomically and functionally homologous to the mammalian enteric nervous system. Here, we show that the I3 pharyngeal enteric neuron responds to cations via an I3-specific variant ionotropic receptor (IR) to regulate salt stress tolerance. The GLR-9 IR, located at the gut lumen-exposed sensory end of I3, is necessary and sufficient for salt sensation, establishing a chemosensory function for IRs beyond insects. Salt detection by I3 protects specifically against high salt stress, as glr-9 mutants show reduced tolerance of hypertonic salt but not sugar solutions, with or without prior acclimation. While cholinergic signaling from I3 promotes tolerance to acute high salt stress, peptidergic signaling from I3 during acclimation is essential for resistance to a subsequent high salt challenge. Transcriptomic analyses show that I3 regulates salt tolerance in part via regulating the expression of osmotic stress response genes in distal tissues. Our results describe the mechanisms by which chemosensation mediated by a defined enteric neuron regulates physiological homeostasis in response to a specific abiotic stress.

neuroscience↗

bioRxiv2025

GH25 lysozyme mediates tripartite interkingdom interactions and microbial competition on the plant leaf surface

Microbial communities inhabiting plants have emerged as crucial factors in regulating plant health and defense against disease-causing pathogens. The basidiomycete yeast Moesziomyces bullatus ex. Albugo on Arabidopsis (MbA) releases Glycoside Hydrolase 25 (GH25) protein which regulates the leaf microbiome by antagonizing an oomycete A. laibachii biotrophic pathogen MbA. Application of both MbA and GH25 protein rescued fresh shoot weight of A. thaliana upon A. laibachii infection, showing its potential in plant protection. Tripartite interaction assays did not reveal antagonistic activity of GH25 towards other plant pathogenic oomycetes or fungi besides A. laibachii. We identified a core set of bacteria are closely associated with A. laibachii and established that GH25 inhibits members of this core group. Among A. laibachii-associated bacteria that were inhibited by GH25, Curtobacterium sp. could override the inhibition of A. laibachii by MbA. We describe a tripartite antagonistic interaction in which bacterium and oomycete protect each other from growth inhibition by MbA. Curtobacterium sp., in turn, exhibits specific inhibition of A. laibachii-associated bacteria that are not targeted by MbA but themselves antagonize A. laibachii. Our study reveals an inter-kingdom interaction network in which a GH25 lysozyme shapes the antagonistic relationship between yeast, a pathogenic oomycete and an oomycete-associated bacterium.

microbiology↗

bioRxiv2025

CRISPR-Cas9 Targeting of G-Quadruplex DNA in ADH1 promoter Highlights its role in Transcriptome and Metabolome Regulation

G-quadruplex (G4) structures are critical regulators of gene expression, yet the role of an individual G4 within its native chromatin remains underexplored. Here, we used CRISPR-Cas9 to introduce guanine-to-thymine mutations at a G4-forming motif within the adh1+ promoter in yeast, creating two mutant strains: one with G4-only mutations and another with both G4 and TATA-box mutations. Chromatin immunoprecipitation using BG4 antibody confirmed reduced G4 enrichment in both mutants, validating G4 structure formation in the wild-type chromatin. Detailed characterizations demonstrated that the G4 mutations alter its dynamics without fully preventing its formation. These mutations significantly reduce adh1 transcript levels, with G4 TATA-box mutant causing the strongest transcriptional suppression. This indicates a positive regulatory role for the Adh1 G4 structure in adh1+ gene expression. Furthermore, both mutants displayed altered transcriptomic profiles, particularly impacting the oxidoreductase pathway. Metabolomic analyses by mass spectrometry further highlighted substantial disruptions in NAD+/NADH metabolism, a key energy reservoir for metabolic regulation. Together, our findings illustrate how deregulation of a single G4 structure influences transcriptome regulation, with implications for metabolic diseases. It also highlights the therapeutic potential of G4 modulation as a novel, controlled approach to reprogram cellular metabolism to achieve targeted phenotypic shifts. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/643214v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@10262a6org.highwire.dtl.DTLVardef@19aa1a2org.highwire.dtl.DTLVardef@e99487org.highwire.dtl.DTLVardef@11639e5_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Unveiling Hidden Microbial Diversity in Mars2020 Mission Assembly Cleanrooms withMolecular Insights into the Persistent andPerseverance of Novel Species DefyingMetagenome Sequencing

NASA cleanrooms, where space mission components are assembled, maintain stringent cleaning protocols and nutrient-poor environments, resulting in low yet persistent microbial loads. Although these oligotrophic extremophiles are reported in small numbers, their resistance to environmental stresses, sparse presence, and difficulty in extracting biomolecules often lead to their omission, even with advanced sequencing technologies. Traditional metagenomic approaches fail to detect these rare species due to challenges in lysing robust microbial cells and isolating minute amounts of DNA from dominant microorganisms. Additionally, the absence of database references for novel extremophiles limits their identification. Over a six month period of monitoring Mars 2020 mission cleanrooms, 182 bacterial strains from 19 families were identified using advanced molecular techniques. This included 14 novel Gram-positive species, eight of which were spore-formers. Despite being present at only about 0.001% abundance in metagenomic sequencing data, they were successfully cultured. Functional studies revealed their capabilities in nitrogen cycling, carbohydrate metabolism, and radiation resistance. Furthermore, 12 biosynthetic gene clusters, including those linked to ectoine and{varepsilon} -poly-L-lysine production, underscore their biotechnological potential. These findings emphasize the hidden microbial diversity in spacecraft assembly cleanrooms and highlight the need for advanced detection methods to uncover extremophiles with potential applications in biotechnology and space exploration. SynopsisUnderstanding extremophiles in NASA spacecraft assembly cleanrooms aids contaminant management in confined habitats, ensuring sustainability and safety in future space missions.

genomics↗

bioRxiv2024

FROG Analysis Ensures the Reproducibility of Genome Scale Metabolic Models

Genome-scale metabolic models (GEMs) and other constraint-based models (CBMs) play a pivotal role in understanding biological phenotypes and advancing research in areas like metabolic engineering, human disease modelling, drug discovery, and personalized medicine. Despite their growing application, a significant challenge remains in ensuring the reproducibility of GEMs, primarily due to inconsistent reporting and inadequate model documentation of model results. Addressing this gap, we introduce FROG analysis, a community-driven initiative aimed at standardizing reproducibility assessments of CBMs and GEMs. The FROG framework encompasses four key analyses--Flux variability, Reaction deletion, Objective function, and Gene deletion--to produce standardized, numerically reproducible FROG reports. These reports serve as reference datasets, enabling model evaluators, curators, and independent researchers to verify the reproducibility of GEMs systematically. BioModels, a leading repository of systems biology models, has integrated FROG analysis into its curation workflow, enhancing the reproducibility and reusability of submitted GEMs. In our study evaluating 65 GEM submissions from the community, approximately 40% reproduced without intervention, 28% requiring minor adjustments, and 32% needing input from authors. The standardization introduced by FROG analysis facilitated the detection and resolution of issues, ultimately leading to the successful reproduction of all models. By establishing a standardized and comprehensive approach to evaluating GEM reproducibility, FROG analysis significantly contributes to making CBMs and GEMs more transparent, reusable, and reliable for the broader scientific community.

systems biology↗

bioRxiv2024

Differential modulation of sensory response dynamics by cilia structure and intraflagellar transport within and across chemosensory neurons

Sensory neurons contain morphologically diverse primary cilia that are built by intraflagellar transport (IFT) and house sensory signaling molecules. Since both ciliary structural and signaling proteins are trafficked via IFT, it has been challenging to decouple the contributions of IFT and cilia structure to neuronal responses. By acutely inhibiting IFT without altering cilia structure and vice versa, here we describe the differential roles of ciliary trafficking and sensory ending morphology in shaping chemosensory responses in C. elegans. We show that a minimum cilium length but not continuous IFT is necessary for a subset of responses in the ASH nociceptive neurons. In contrast, neither cilia nor continuous IFT are necessary for odorant responses in the AWA olfactory neurons. Instead, continuous IFT differentially modulates response dynamics in AWA. Upon acute inhibition of IFT, cilia-destined odorant receptors are shunted to ectopic branches emanating from the cilia base. Spatial segregation of receptors in these branches from a cilia-restricted regulatory kinase results in odorant desensitization defects, highlighting the importance of precise organization of signaling molecules at sensory endings in regulating response dynamics. We also find that adaptation of AWA responses upon repeated exposure to an odorant is mediated by IFT-driven removal of its cognate receptor, whereas adaptation to a second odorant is regulated via IFT-independent mechanisms. Our results reveal unexpected complexity in the contribution of IFT and cilia organization to the regulation of responses even within a single chemosensory neuron type, and establish a critical role for these processes in the precise modulation of olfactory behaviors.

neuroscience↗

bioRxiv2023

Feedforward and feedback mechanisms cooperatively regulate rapid experience-dependent response adaptation in a single thermosensory neuron type

Sensory adaptation allows neurons to adjust their sensitivity and responses based on recent experience. The mechanisms that mediate continuous adaptation to stimulus history over seconds to hours long timescales, and whether these mechanisms can operate within a single sensory neuron type, are unclear. The single pair of AFD thermosensory neurons in C. elegans exhibits experience-dependent plasticity in their temperature response thresholds on both minutes- and hours-long timescales upon a temperature upshift. While long-term response adaptation requires changes in gene expression in AFD, the mechanisms driving rapid response plasticity are unknown. Here, we show that rapid thermosensory response adaptation in AFD is mediated via cGMP and calcium-dependent feedforward and feedback mechanisms operating at the level of primary thermotransduction. We find that either of two thermosensor receptor guanylyl cyclases (rGCs) alone is sufficient to drive rapid adaptation, but that each rGC drives adaptation at different rates. rGC-driven adaptation is mediated in part via phosphorylation of their intracellular domains, and calcium-dependent feedback regulation of basal cGMP levels via a neuronal calcium sensor protein. In turn, cGMP levels feedforward via cGMP-dependent protein kinases to phosphorylate a specific subunit of the cGMP-gated thermotransduction channel to further regulate rapid adaptation. Our results identify multiple molecular pathways that act in AFD to ensure rapid adaptation to a temperature change, and indicate that the deployment of both transcriptional and non-transcriptional mechanisms within a single sensory neuron type can contribute to continuous sensory adaptation. Significance statementThe nervous system must continuously adapt to the sensory environment in order to adjust response sensitivity. Although both short- and long-term response adaptation has been reported to occur within sensory neurons themselves, how temporally distinct plasticity mechanisms are coordinated within single sensory neurons is unclear. We previously showed that long-term adaptation of temperature responses in the single AFD thermosensory neuron pair in C. elegans is mediated via gene expression changes in this neuron type. Here we show that multiple second messenger-driven feedforward and feedback mechanisms act to drive rapid thermosensory adaptation in AFD. Our results indicate that modulation of thermotransduction molecules via both transcriptional and non-transcriptional mechanisms contribute to distinct temporal phases of adaptation in a single sensory neuron type.

neuroscience↗

bioRxiv2023

Genomic, Functional, and Metabolic Enhancements in Multidrug-Resistant Enterobacter bugandensis Facilitating its Persistence and Succession in the International Space Station

BackgroundThe International Space Station (ISS) stands as a testament to human achievement in space exploration. Despite its highly controlled environment, characterised by microgravity, increased CO2 levels, and elevated solar radiation, microorganisms occupy a unique niche. These microbial inhabitants play a significant role in influencing the health and well-being of astronauts on board. One microorganism of particular interest in our study is Enterobacter bugandensis, primarily found in clinical specimens including the human gastrointestinal tract, and also reported to possess pathogenic traits, leading to a plethora of infections. ResultsDistinct from their Earth counterparts, ISS E. bugandensis strains have exhibited resistance mechanisms that categorize them within the ESKAPE pathogen group, a collection of pathogens recognized for their formidable resistance to antimicrobial treatments. During the two-year Microbial Tracking 1 mission, 12 strains of multidrug resistant E. bugandensis were isolated from various locations within the ISS. We have carried out a comprehensive study to understand the genomic intricacies of ISS-derived E. bugandensis in comparison to terrestrial strains, with a keen focus on those associated with clinical infections. We unravel the evolutionary trajectories of pivotal genes, especially those contributing to functional adaptations and potential antimicrobial resistance. A hypothesis central to our study was that the singular nature of the stresses of the space environment, distinct from any on Earth, could be driving these genomic adaptations. Extending our investigation, we meticulously mapped the prevalence and distribution of E. bugandensis across the ISS over time. This temporal analysis provided insights into the persistence, succession, and potential patterns of colonization of E. bugandensis in space. Furthermore, by leveraging advanced analytical techniques, including metabolic modelling, we delved into the coexisting microbial communities alongside E. bugandensis in the ISS across multiple missions and spatial locations. This exploration revealed intricate microbial interactions, offering a window into the microbial ecosystem dynamics within the ISS. ConclusionsOur comprehensive analysis illuminated not only the ways these interactions sculpt microbial diversity but also the factors that might contribute to the potential dominance and succession of E. bugandensis within the ISS environment. The implications of these findings are two-fold. Firstly, they shed light on microbial behavior, adaptation, and evolution in extreme, isolated environments. Secondly, they underscore the need for robust preventive measures, ensuring the health and safety of astronauts by mitigating risks associated with potential pathogenic threats.

systems biology↗

bioRxiv2023

Host ZCCHC3 blocks HIV-1 infection and production by a dual mechanism

Most mammalian cells prevent viral infection and proliferation by expressing various restriction factors and sensors that activate the immune system. While anti-human immunodeficiency virus type 1 (HIV-1) host restriction factors have been identified, most of them are antagonized by viral proteins. This has severely hindered their development in anti-HIV-1 therapy. Here, we describe CCHC-type zinc-finger-containing protein 3 (ZCCHC3) as a novel anti-HIV-1 factor that is not antagonized by viral proteins. ZCCHC3 suppresses production of HIV-1 and other retroviruses. We show that ZCCHC3 acts by binding to Gag nucleocapsid protein via zinc-finger motifs. This prevents interaction between the Gag nucleocapsid protein and viral genome and results in production of genome-deficient virions. ZCCHC3 also binds to the long terminal repeat on the viral genome via the middle-folded domain, sequestering the viral genome to P-bodies, which leads to decreased viral replication and production. Such a dual antiviral mechanism is distinct from that of any other known host restriction factors. Therefore, ZCCHC3 is a novel potential target in anti-HIV-1 therapy.

microbiology↗