Biology subjects

Bhat, A.

Publications and source records attributed to Bhat, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Higher-order metabolic interactions among oral commensals gate pathobiont expansion through succinate-driven pH modulation

Despite advances in defining microbiome shifts associated with inflammatory mucosal diseases, the ecological interactions that constrain or facilitate pathobiont expansion remain poorly understood. Using a six-species synthetic oral microbial community and factorial interaction screening, we identified a higher-order interaction governing the growth of the periodontal pathobiont Porphyromonas gingivalis. The core community member Veillonella parvula was the strongest positive determinant of P. gingivalis growth, but this effect was substantially reduced by the health-associated commensal Actinomyces oris. A. oris-mediated antagonism resulted from extracellular acidification and was enhanced under anaerobic conditions. Genetic dissection of A. oris fermentation revealed that lactate dehydrogenase (ldh1) contributes to anaerobic lactate production, but ldh1 deletion only partially relieved P. gingivalis inhibition. Instead, succinate, produced through a succinate dehydrogenase/fumarate reductase pathway (sdh2), emerged as the principal driver of acidification and P. gingivalis suppression. At high cell densities, however, V. parvula consumed both lactate and succinate, reversing acidification and restoring conditions permissive for P. gingivalis growth. To assess the relevance of these interactions in vivo, we analyzed subgingival microbiome from 1,355 adults, including 555 with detectable P. gingivalis. Among these individuals, P. gingivalis abundance was negatively associated with Actinomyces abundance after adjustment for periodontitis severity, whereas this association was attenuated at high V. parvula abundance, consistent with the interaction observed in vitro. Together, these findings identify succinate as a previously unrecognized mediator of interbacterial antagonism and reveal how higher-order metabolic interactions among oral commensals regulate pathobiont expansion through pH modulation, with protective effects shaped by oxygen availability and metabolic cross-feeding.

microbiology↗

bioRxiv2026

Clustering of the Adhesion-GPCR Latrophilin-3 Drives Excitatory Synapse Assembly

Precise control of synapse formation is essential for brain function. Adhesion-GPCRs combine adhesion, signaling, and scaffold recruitment to regulate synapse formation, yet their mechanisms of action remain unclear. Here, we identify nanoscale clustering of the adhesion-GPCR Latrophilin-3 as a key mechanism regulating excitatory synapse assembly. We find that endogenous Latrophilin-3 forms densely packed nanoclusters, with larger nanoclusters enriched at excitatory synapses. To probe the functional significance of Latrophilin-3 clustering, we engineered an optogenetically controlled Latrophilin-3. Light-induced Latrophilin-3 clustering triggered robust excitatory synapse formation, which required both Latrophilin-3-mediated G-protein signaling and postsynaptic scaffold recruitment. Strikingly, clustering of a mutant Latrophilin-3 lacking known ligand-binding domains still promoted synapse formation, indicating that Latrophilin-3 ligands induce synapse assembly primarily by clustering Latrophilin-3. Our findings suggest a general paradigm by which extracellular ligand-induced clustering activates adhesion-GPCRs by generating compartmentalized signaling, which in the case of Latrophilin-3, cooperates with postsynaptic scaffold recruitment to drive synapse assembly.

neuroscience↗

bioRxiv2026

Mitochondrial NAD+ import gates neuronal resilience to active SARM1

SARM1 is an inducible NADase that executes pathological axon degeneration, but how NAD+ destruction causes neuronal failure remains unclear. Because SARM1 is predicted to act outside the mitochondrial matrix, cytosolic NAD+ loss has been viewed as the critical lethal lesion. We show that SARM1 activation rapidly depletes cytosolic and mitochondrial NAD+ and collapses ATP in both compartments, revealing early, coupled metabolic failure. Enhancing mitochondrial NAD+ import through SLC25A51, the mitochondrial NAD+ transporter, preserves mitochondrial NAD+, maintains mitochondrial function, and delays axon degeneration and neuronal death despite ongoing SARM1 activity. Unexpectedly, SLC25A51 restores cytosolic NAD+-dependent metabolism, reversing a glycolytic block and increasing NAD+ synthesis during stress. Glycolytic inhibition attenuates protection, identifying cytosolic metabolic recovery as an important component of neuronal resilience. AAV-SLC25A51 improves function in a chronic SARM1-dependent neuropathy model. Thus, mitochondrial NAD+ import gates SARM1-driven degeneration by limiting coupled mitochondrial-cytosolic metabolic failure, presenting a downstream intervention point for axon preservation.

neuroscience↗

bioRxiv2026

Autonomous AI-Driven Nanoscale Spatial Mapping Reveals Novel Targets and Ternary Architectures in 5xFAD Alzheimer's Disease Model

Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta (A{beta}) and microtubule-associated protein tau (MAPT) neurofibrillary tangles in the brain; however, the molecular mechanisms underlying associated synaptic dysfunction remain unclear. Eratos' AI for Spatial Computing and Embedded Neurotherapeutic Discovery (ASCENDTM) engine was employed to analyze multiplexed expansion revealing (multiExR) data from the 5xFAD and wild-type mouse somatosensory cortex, enabling quantitative mapping of A{beta}, RIM1, and GluA2 nanodomains. ASCENDTM identified significant and previously unreported protein associations, including nanoscale colocalization of A{beta} with postsynaptic AMPA-receptor subunit GluA2 and amyloid-bridged A{beta}-GluA2-RIM1 ternary assemblies. These spatial signatures indicate complex synaptic disruption, defined by distinct morphological and density profiles associated with neurobiological and neuroinflammatory pathology. Integrating high-dimensional spatial computing with cross-modal literature synthesis advances traditional microscopy analysis toward autonomous, AI-driven scientific discovery. Identifying novel, druggable interfaces within native tissue expedites the discovery of precision neurotherapeutics for AD and other complex central nervous system disorders.

systems biology↗

bioRxiv2026

Convergent anti-MRSA potency across compositionally distinct essential oils: a chemotype similarity index for strain-dependent chemistry-activity analysis

Antimicrobial resistance represents a continuing threat to clinical infection management, with methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli identified by the World Health Organization as priority pathogens. This study evaluated the antimicrobial activity, synergistic potential, and chemical composition of six plant-derived preparations -- three ethanolic extracts (nettle, thyme, rosemary) and three essential oils (lavender, lemongrass, doTERRA Peace blend) -- against MRSA, methicillin-sensitive S. aureus (MSSA), and E. coli K-12 by disc diffusion, broth microdilution, post-exposure culturability, antimicrobial interactions assessed by checkerboard assay, and GC-MS profiling. Disc diffusion produced no interpretable zones of inhibition for any plant preparation tested, however broth microdilution revealed reproducible inhibitory activity within published ranges across the panel. Three essential oils achieved a median Minimum Inhibitory Concentration (MIC) of 0.39 mg/mL against MRSA despite presenting compositionally distinct chemotypes -- lavender was linalool-dominated (61% combined), lemongrass was citral-dominated (76%), and the doTERRA blend was sesquiterpene-rich. Rosemary ethanolic extract achieved the same potency (0.39 mg/mL) against MSSA. No preparation produced a bactericidal reduction ([≥]3 log CFU mL-{superscript 1}) at any timepoint, with all reductions transient and recovering by 24 hours. Checkerboard combinations of plant preparations with vancomycin and ciprofloxacin were uniformly classified, according to the Fractional Inhibitory Concentration Index (FICI), as indifference/no interaction, attributable in part to inoculum-mediated effects on vancomycin MIC. To analyse the relationship between chemical composition and antimicrobial outcomes, we introduce a Chemotype Similarity Index (CSI), a chemometric framework quantifying pairwise compositional similarity between essential oils by Pearson correlation and relating it to log2-MIC differences across strains. CSI revealed a strain-dependent chemistry-activity relationship -- convergent against MRSA, monotonic against MSSA, and absent against E. coli -- indicating that compositional similarity predicts antimicrobial outcomes on a strain-specific basis. The convergence of three chemotypically divergent essential oils with the same anti-MRSA potency suggested a shared membrane-disrupting mechanism operating through distinct chemical routes. Although exploratory at this scale, the CSI framework provides a reusable analytical scaffold for linking phytochemical composition to antimicrobial activity, and identifies the MRSA convergence as a specific direction for mechanistic investigation into the development of plant-derived antimicrobial adjuncts.

microbiology↗

bioRxiv2026

Hornbill abundance and habitat correlates in Kali Tiger Reserve, Western Ghats, India-Insights from collaborative monitoring

1.The future of species, particularly large-bodied birds, under climate threats, is increasingly unclear. Protected areas (PAs) can mitigate the impacts of global change, but are not completely immune. This makes it imperative to monitor populations even inside PAs. In the forests of the Western Ghats, three hornbill species are found--Malabar Grey Hornbill, Malabar Pied Hornbill and Great Hornbill. Kali Tiger Reserve, of Karnataka state, India, is known for its healthy hornbill populations, yet few systematic surveys have attempted to estimate their abundance, distributions and habitat affiliations. In this study, we documented the distributions of the three hornbills, estimated the density of Malabar Grey Hornbills and assessed correlates of hornbill encounter rates within the reserve. Malabar Grey Hornbills were the most abundant and widely distributed, found in all ranges of the reserve. Gund, Kadra and Phansoli had the most detections of Malabar Pied and Great Hornbills. Encounter rates of Malabar Grey Hornbill were positively correlated with food-tree stem density, those of Malabar Pied Hornbill negatively correlated with basal area, while those of Great Hornbill not significantly associated with any variable. Malabar Grey Hornbills had a density of 5.1 per km2 (mean flock size = 1.2). While encounter rates of Malabar Pied and Great Hornbills were low, these numbers track the breeding season, when vocal activity is low and females are inside nests. This survey represents a partnership between researchers and the Karnataka forest department, aimed towards inculcating the collaborative spirit of research and monitoring.

ecology↗

bioRxiv2025

Active flows drive clustering and sorting of membrane components with differential affinity to dynamic actin cytoskeleton

Several cell membrane proteins, including signalling receptors and cell adhesion receptors, bind to contractile cortical F-actin at the cytoplasmic leaflet. Interaction with contractile actomyosin and associated actin flows drives these proteins into nanoscale clusters and mesoscopic assemblies of physiological relevance. In the context of diverse actin-binding membrane proteins, we ask how a specific composition of the local cluster/assembly may be achieved. Using in vitro reconstitution together with kinetic Monte Carlo simulations our studies reveal that an interplay between differential actin-binding affinity, protein-protein interactions and actomyosin remodelling leads to specific molecular patterning within a cluster and sorting between clusters. We show that in the lamellipodia of spreading cells in vivo, actin flows also result in the sorting of high and low-affinity actin-binders. This affinity-based sorting mechanism provides an attractive means for locally controlling cell membrane composition via engagement with the active cortical meshwork beneath.

cell biology↗

bioRxiv2025

In-vitro Knockdown and Pharmacological Inhibition of RIPK2 Attenuates Calcium Oxalate-Nephrocalcinosis Associated Inflammation and Oxidative Stress in NRK-52E and Primary Renal Epithelial Cells

Ectopic deposition of calcium oxalate in the parenchyma (nephrocalcinosis) or as stones in the collecting system (nephrolithiasis) causes inflammation and oxidative stress in renal tissue. Receptor interacting serine/threonine kinase 2 (RIPK2) is a well-known mediator of oxidative stress and inflammation. However, its role in nephrocalcinosis or nephrolithiasis remains unexplored. NRK-52E and primary renal cells were treated with calcium oxalate-monohydrate (COM) to induce nephrocalcinosis like pathological changes. siRNAs and commercially available inhibitor was used to block RIPK2s activity. Oxidative stress, inflammation, apoptosis, crystal adhesion, and changes in cell morphology were measured as endpoint markers. Exposure to COM but not to adenine, H2O2, and high-glucose significantly upregulated RIPK2 levels and induced oxidative stress, intracellular-calcium overload, and mitochondrial dysfunction. This was accompanied by the activation of NF-{kappa}B pathway, high levels of pro-inflammatory and low levels of anti-inflammatory cytokines, increased apoptosis, and epithelial-mesenchymal transition (EMT). RIPK2 silencing or pharmacological inhibition effectively mitigated these pathological changes and restored levels of antioxidant enzymes. Mechanistically, RIPK2 inhibition disrupted the NF-{kappa}B/TGF-{beta}1 signaling and reduced CaOx crystal adhesion. Preliminary data from our previously conducted in vivo CaOx mouse model study confirmed the CaOx-induced RIPK2 upregulation. Our data strongly supports the involvement of RIPK2 in CaOx-induced renal cell damage.

pharmacology and toxicology↗

bioRxiv2025

Inactivation of the Fusobacterium nucleatum Rnf complex reduces FadA-mediated amyloid formation and tumor development

The Gram-negative anaerobe Fusobacterium nucleatum is an oral oncobacterium that promotes colorectal cancer (CRC) development with the amyloid-forming cell surface adhesin FadA integral to CRC tumorigenesis. We describe here molecular genetic studies uncovering a novel mode of metabolic regulation of FadA-mediated tumor formation by a highly conserved respiratory enzyme known as the Rnf complex. First, we show that genetic disruption of Rnf, via rnfC deletion, significantly reduces the level of fadA transcript, accompanied by a near-complete abolishment of the precursor form of FadA (pFadA), reduced assembly of FadA at the mature cell pole, and severe defects in the osmotic stress-induced formation of FadA amyloids. We show further that the Rnf complex regulates three response regulators (CarR, ArlR, and S1), which modulate the expression of pFadA, without affecting fadA transcript. Consistent with our hypothesis that these response regulators control factors that process FadA, deletion of rnfC, carR, arlR, or s1 each impairs expression of the signal peptidase gene lepB, and FadA production is nearly abolished by CRISPR-induced depletion of lepB. Importantly, while rnfC deletion does not affect the ability of the mutant cells to adhere to CRC cells, rnfC deficiency significantly diminishes the fusobacterial invasion of CRC cells and formation of spheroid tumors in vitro. Evidently, the Rnf complex modulates the expression of the FadA adhesin and tumorigenesis through a gene regulatory network consisting of multiple response regulators, each controlling a signal peptidase that is critical for the post-translational processing of FadA and surface assembly of FadA amyloids. IMPORTANCEThe Rhodobacter nitrogen-fixation (Rnf) complex of Fusobacterium nucleatum plays an important role in the pathophysiology of this oral pathobiont, since genetic disruption of this conserved respiratory enzyme negatively impacts a wide range of metabolic pathways, as well as bacterial virulence in mice. Nonetheless, how Rnf deficiency weakens the virulence potential of F. nucleatum is not well understood. Here, we show that genetic disruption of the Rnf complex reduces surface assembly of adhesin FadA and FadA-mediated amyloid formation, via regulation of signal peptidase LepB by multiple response regulators. As FadA is critical in the carcinogenesis of colorectal cancer (CRC), the ability to invade CRC cells and promote spheroid tumor growth is strongly diminished in an Rnf-deficient mutant. Thus, this work uncovers a molecular linkage between the Rnf complex and LepB-regulated processing of FadA - likely via metabolic signaling - that maintains the virulence potential of this oncobacterium in various cellular niches.

microbiology↗

bioRxiv2024

Vocal species are more central in Eastern Himalayan Mixed-Species bird flocks

Mixed-species flocks (MSF) represent an important form of social organisation in bird communities worldwide. Despite its likely importance in flock formation and cohesion, the role of vocal communication in the formation and maintenance of MSF in birds is hitherto understudied. In this study, we examine if a species centrality within a mixed-species flock is influenced by its vocal behaviour during the dawn chorus, i.e., the time of MSF formation. Using acoustic sampling and field observations, we studied the bird species found in MSF in the Eastern Himalayas. Our results show differential vocal activity patterns among MSF-forming bird species and suggest a positive correlation between calling rates and closeness centrality (species importance in a flock) in understory MSFs. We also found a more synchronised vocalisation pattern in the understory MSFs, with a consistent peak in vocal activity in the early morning hours, whereas no consistent vocal pattern was found for canopy flocks. Overall, our results suggest a potential mechanism that drives MSF formation wherein the vocal activity of central species precedes and likely attracts participation from other attendant species.

ecology↗

bioRxiv2024

Plant genotype and microbial strain combinations strongly influence the transcriptome under heavy metal stress conditions

Heavy metals such as cadmium (Cd) and mercury (Hg) pose significant threats to plant health and food safety as they are absorbed from the environment. Legumes are generally considered sensitive to heavy metals but possess standing genetic variation for accumulation and tolerance to toxic ions. We conducted a transcriptomic analysis on hydroponically and soil grown Medicago truncatula plants to investigate gene expression responses to Cd and Hg exposure in roots, leaves, and nodules. By using plant genotypes with varying metal tolerance or accumulation levels, we observed distinct clustering of gene ontologies, indicating tissue-specific, genotype-specific, and metal-specific gene expression patterns. Considering the symbiotic relationship between legumes and nitrogen-fixing bacteria, we further examined plant phenotypes and transcriptomes of plant genotypes with contrasting Hg accumulation levels and inoculated them with high or low Hg-tolerant Sinorhizobium medicae strains that have presence-absence variation for a mercury reductase (Mer) operon. Host plants inoculated with the Hg-tolerant rhizobia strain possessing a Mer operon exhibited less reduction in nodule number and plant biomass. A smaller reduction in iron (Fe) distribution in nodules after Hg stress was measured using X-ray Fluorescence (XRF) imaging. Dual transcriptome (host plant and bacteria) analysis of nodules revealed a remarkable decrease in the number of differentially expressed genes (DEGs) and clustering of gene ontologies in plants inoculated with the Hg-tolerant rhizobia strain, including symbiosis related genes. This suggests the Hg-tolerant rhizobia strain has the potential to mitigate Hg stress in host plants. Furthermore, we observed genotype-by-genotype interactions between the high Hg accumulating plant genotype and the Hg-tolerant rhizobia strain. These findings provide insights into enhancing plant resilience in contaminated environments through optimizing legume-rhizobia interactions for heavy metal tolerance, as well as identification of genetic mechanisms that can reduce transport to edible plant parts. HighlightsO_LIGenetic variation in tolerance to heavy metals affects responses in plant tissues C_LIO_LISymbiosis with Hg tolerant rhizobia strain reduced stress response in host plant C_LIO_LIDual-transcriptomics in nodules identified metal stress and symbiosis responses C_LIO_LIGenotype by genotype interaction significantly affected symbiosis gene expression C_LIO_LIRhizobia strain possessing Mer operon suggests genetic basis affecting responses C_LI

plant biology↗

bioRxiv2024

Myosin cluster dynamics determines epithelial wound ring constriction

Collection of myosin motors and actin filaments can self-assemble into submicrometric clusters under the regulation of RhoA. Emergent dynamics of these clusters have been reported in a variety of morphogenetic systems, ranging from Drosophila to acto-myosin assays in vitro. In single cell cytokinetic rings, acto-myosin clusters are associated with stress generation when radial and transport when tangential with respect to the ring closure. Here, we show that these phenomena hold true for acto-myosin multi-cellular rings during wound closure in epithelial monolayers. We assessed the activity of RhoA using FRET sensors, and we report that cluster dynamics does not correlate with RhoA activity. Nevertheless, we show that bursts of RhoA activation precede recruitment of myosin. Altogether myosin clusters dynamics is conserved between single and multi-cellular systems and this suggests that they could be used as generic read-outs for mapping and predicting stress generation and shape changes in morphogenesis.

biophysics↗

bioRxiv2024

fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans

Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five C. elegans FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of C. elegans fmo-4 promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of fmo-4 in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of fmo-4 expression. Highlighting the importance of calcium homeostasis in this pathway, fmo-4 overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/fmo-4 interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of fmo-4 and/or interact with fmo-4 to affect lifespan and stress resistance. Further analysis supports a pathway where fmo-4 modulates calcium homeostasis downstream of activating transcription factor-6 (atf-6), whose knockdown induces and requires fmo-4 expression. Together, our data identify fmo-4 as a longevity-promoting gene whose actions interact with known longevity pathways and calcium homeostasis.

genetics↗

bioRxiv2024

Improved prediction of stabilizing mutations in proteins by incorporation of mutational effects on ligand binding

While many computational methods accurately predict destabilizing mutations, identifying stabilizing mutations has remained a challenge, due to their relative rarity. We tested {Delta}{Delta}G0 predictions from computational predictors such as Rosetta, ThermoMPNN, RaSP, and DeepDDG, using eighty-two mutants of the bacterial toxin CcdB as a test case. On this dataset, the best computational predictor is ThermoMPNN which identifies stabilizing mutations with a precision of 68%. However, the average increase in Tm for these predicted mutations was only 1{degrees}C for CcdB, and predictions were poorer for a more challenging target, influenza neuraminidase. Using data from multiple previously described yeast surface display libraries and in vitro thermal stability measurements, we trained logistic regression models to identify stabilizing mutations with a precision of 90% and an average increase in Tm of 3{degrees}C for CcdB. When such libraries contain a population of mutants with significantly enhanced binding relative to the corresponding wild type, there is no benefit in using computational predictors. It is then possible to predict stabilizing mutations without any training, simply by examining the distribution of mutational binding scores. This avoids laborious steps of in vitro expression, purification, and stability characterization. When this is not the case, combining data from computational predictors with high-throughput experimental binding data enhances the prediction of stabilizing mutations. However, this requires training on stability data measured in vitro with known stabilized mutants. It is thus feasible to predict stabilizing mutations rapidly and accurately for any system of interest that can be subjected to a binding selection or screen.

biophysics↗

bioRxiv2023

Local adaptation to mercury contamination by nitrogen-fixing rhizobia is driven by horizontal gene transfer, copy number, and enhanced gene expression

Mercury (Hg) is highly toxic and has the potential to cause severe health problems for foraging animals and humans when transported into edible plant parts. Soil rhizobia that form symbiosis with legumes may possess mechanisms to prevent heavy metal translocation from roots to shoots in plants by exporting metals from nodules or compartmentalizing metal ions inside nodules. Using long-read sequencing, we assembled the genomes of Sinorhizobium medicae and Rhizobium leguminosarum from the Almaden mercury mine in Spain with high variation in Hg-tolerance to identify structural and transcriptomic differences between low and high Hg-tolerant strains. While independent mercury reductase A (merA) genes are prevalent in -proteobacteria, Mer operons are rare and often vary in their gene organization. Our analyses identified multiple structurally conserved merA homologs in the genomes of S. medicae, including a dihydrolipoamide 2-oxoglutarate dehydrogenase (D2OD), but only the strains that possessed a Mer operon exhibited hypertolerance to Hg. Using RNAseq reads mapped to the unique genome assemblies, we found the Hg-tolerant strains which possessed a Mer operon, that nearly all genes within the operon were significantly up-regulated in response to Hg stress in free-living conditions and in nodules. In both free-living and nodule environments, we found the Hg-tolerant strains with a Mer operon exhibited the fewest number of DEGs in the genome, indicating a rapid and efficient detoxification of Hg2+ from the cells that reduced general stress responses to the Hg-treatment. Expression changes in S. medicae while inside of nodules showed that both rhizobia strain and host-plant tolerance affected the number of DEGs. Aside from Mer operon genes, nif genes which are involved in nitrogenase activity in S. medicae showed significant up-regulation in the most Hg-tolerant strain while inside the most Hg-accumulating host-plant, indicating a genotype-by-genotype interaction that influences nitrogen-fixation under stress conditions. Transfer of the Mer operon to non-tolerant strains resulted in an immediate increase in Hg tolerance, indicating that the operon is solely necessary to confer hypertolerance to Hg, despite paralogous merA genes present elsewhere in the genome. This study demonstrated that the Mer operon can be exchanged via horizontal gene transfer into non-tolerant rhizobia strains naturally and experimentally.

microbiology↗

bioRxiv2023

A diet of oxidative stress-adapted bacteria improves stress resistance and lifespan in C. elegans via p38-MAPK.

Organisms across taxa are exposed to stresses such as variable temperature, redox imbalance, and xenobiotics. Successfully responding to stress and restoring homeostasis is crucial for viability of the organism. During aging, the ability to effectively respond to stress declines, contributing to development of disease. In many multicellular animals, aging also coincides with changes in the microbiome that can contribute to disease-states. Because animals and their microbiota coexist in the same broad environment, they each must adapt to similar stresses. However, the short generation time of microbes leads to faster evolution, allowing the possibility that microbial stress adaptation may influence host physiology. Here we leverage a simplified model involving the nematode C. elegans and its bacterial diet. Our work highlights how bacterial adaptation to oxidative stress impacts the hosts lifespan and response to stress. Intriguingly, our findings reveal that worms fed with bacteria adapted to withstand oxidative stress exhibit enhanced stress resistance and an extended lifespan. Through whole genome sequencing, genetic assays, and metabolic analysis, this study underscores the pivotal role of the bacterial iron-sulfur pathway in governing host stress resistance and lifespan. We further find that iron in the stress-evolved bacteria boost the worms stress resistance and lifespan through activation of the mitogen-activated protein kinase (MAPK) pathway. In conclusion, this study provides evidence that understanding the evolutionary path of microbial adaptation during stress could be leveraged to slow aging and mitigate age-related decline in health.

molecular biology↗

bioRxiv2023

Hiding in the bush, in fear of a predator! Vegetation and predators influence shoaling among wild zebrafish

Social responses of aquatic group-living organisms are critically dependent on predation risk and vegetation cover in their habitat. To gain insight into how these factors shape their immediate responses, we exposed wild zebrafish shoals to either vegetation, predator cues or both these factors simultaneously. Control treatments were not exposed to the above factors. By analyzing 60 unique shoals across 270 experimental trials, we found that while shoals formed significantly larger subgroups and were significantly more polarized in the presence of predator cues, both these properties decreased when shoals experienced predator cues in presence of vegetation. Furthermore, foraging was significantly lower when predator cues and/or vegetation were present. Tracking of all individuals in treatments devoid of vegetation revealed that: (i) compared to control treatments, individuals within shoals receiving predator cues had a significantly higher probability to continue being in a group and (ii) individuals occupying the front positions deviated lesser from their median position within a shoal as compared to other individuals. Anti-predator responses and foraging are critical for survival and therefore, this study provides important insights into shoal dynamics in changing environments.

animal behavior and cognition↗

bioRxiv2023

Understanding inter-individual social networks in mixed-species bird flocks

Mixed-species flocks (MSFs) are an important form of social organisation in forest bird communities worldwide. MSFs provide participants with the benefits of reduced predation risk and/or enhanced foraging efficiency. Recent work has shown that participation in MSFs confers long-term survival benefits in the face of anthropogenic change. However, our understanding of MSFs mainly comes from studies that examine species-level networks, where each node is a unique species and the edges or connections between nodes are associations/interactions between species. While valuable, such approaches might not allow us to understand and investigate the mechanisms that drive MSF formation and structure because social interactions and their effects occur at the individual-level. Empirical studies on multi-species, individual-level MSF social networks have seldom been undertaken due to the various complexities and logistical challenges involved. In this study, we use mist-netting and colour-ringing followed by a standardised observation protocol to construct individual-level social networks in MSFs at 2000m ASL in Eaglenest Wildlife Sanctuary, Arunachal Pradesh, Eastern Himalaya, India. First, we found two separate flocktypes at our study site, comprising two distinct sets of understorey species. The mechanisms contributing to individual-level co-occurrences are likely to differ between these flocktypes, and with MSFs in the Neotropics. The Rusty-fronted Barwing (the nuclear species of one flocktype) shows spatially disjunct territories for each flock while the Yellow-throated Fulvetta (nuclear species of the other flocktype) shows large spatial overlap in its MSF networks, which is likely driven by non-individual-specific benefits such as predation risk dilution. Further, the addition of associating individuals to the social networks has opposite impacts on the two networks. The addition of Coral-billed Scimitar Babblers to the barwing networks greatly reduces network modularity because the associating individuals bridge two modules of barwings (both spatially and in the social network). On the contrary, territorial Rufous-capped Babblers and Grey-cheeked Warblers increase the modularity of the spatially overlapping fulvetta network. Our study provides novel insights into flock formation mechanisms in the Eastern Himalaya, likely applicable to other multi-species flock systems in the Old World.

ecology↗