Biology subjects

Rathore, S.

Publications and source records attributed to Rathore, S..

11 recordsLinked to original sources

bioRxiv2026

Biocontrol efficacy of 2-pyrroldione-5-carboxylic acid (2Py-5CA), an antifungal bioactive macromolecule from the endophyte Penicillium oxalicum, against Ramularia collo-cygni in barley

Global crop production suffers significant losses (23%) due to disease caused by fungal pathogens. Biocontrol agents may be sustainable alternatives to fungicides for disease management. Ramularia leaf spot (RLS), caused by Ramularia collo-cygni (RCC), is a widespread disease of barley (Hordeum vulgare). Two Penicillium oxalicum isolates identified from a collection of endophytes from wild barley, suppress development of R. collo-cygni and exhibit functional plant growth attributes in vitro. Analysis of the P. oxalicum culture filtrate revealed antifungal activity common to both isolates. An untargeted metabolomics (LC-MS/MS) approach uncovered the secondary metabolite profile of the P. oxalicum endophytes including the identification of 2Py-5CA as an antifungal. AntiSMASH-based genome mining identified a non-ribosomal peptide synthetase (NRPSs) biosynthetic gene cluster in P. oxalicum responsible for producing paraherquamide and ultimately the antifungal 2Py-5CA. In vitro studies demonstrated that 2Py-5CA can also suppress growth of the cereal pathogens; Zymoseptoria tritici, Pyrenophora teres, Fusarium graminearum and the horticultural pathogen, Botrytis cinerea disrupting the growth of pathogenic fungal hyphae and spore structure development. Finally, 2Py-5CA reduced RLS symptoms when sprayed on barley seedlings. Therefore 2Py-5CA has potential as a biofungicide to combat fungal crop pathogens. Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=55 SRC="FIGDIR/small/701693v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@9d1bf2org.highwire.dtl.DTLVardef@95bc91org.highwire.dtl.DTLVardef@8f0313org.highwire.dtl.DTLVardef@1130b0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2025

A microbiome-derived transfer RNA modification underlies behavioral optimums and predator avoidance in mosquito larvae

The gut microbiome is a rich source of nutrients that are critical to the development and biology of eukaryotes. Transfer RNAs (tRNAs) are essential components of protein synthesis, and some chemical modifications to tRNA rely on the availability of microbiome-derived nutrients. In eukaryotes, the micronutrient queuosine (Q) is salvaged from the microbiome or diet and then incorporated into eukaryotic tRNA to influence the speed and efficiency of protein synthesis. Here, we examine the role of microbiome-derived Q in mosquito larval development and behavior. When mosquito larvae are grown with a microbiome incapable of synthesizing Q, there is a significant impact on tyrosine levels and processes, which correlate with defects in behavior and cuticle formation. Due to defects in movement and behavioral responses, Q-deficient larvae demonstrate impaired predator evasion, leading to higher instances of capture by predaceous beetle larvae. The broad effects of Q-deficiency in mosquito larvae highlight the importance of microbiome-derived nutrients for eukaryotic physiology and behavior.

physiology↗

bioRxiv2024

Cataract induction in an arthropod reveals how lens crystallins contribute to the formation of biological glass

Lenses are vital components of eyes, crafted through the precise arrangement of proteins to achieve transparency and focusing power, and placed appropriately within the eye for the retina to receive sharp, focused images. Maintaining these states is challenging due to substantial post-embryonic eye and lens growth. Here, we gain insights into required processes by exploring consequences of silencing Lens3, a key lens protein, during growth in Thermonectus marmoratus sunburst diving beetle larvae. We show that lens3RNAi leads to opaque aggregates reminiscent of vertebrate lens cataracts, causing the projection of degraded images which impact behaviour in low light. Our findings uncover how complex biological lenses are constructed and further support that visual input is inconsequential for coordinated eye growth in this clade. We highlight the utility of this insect as a tractable model system to investigate the aetiology of lens cataracts and refractive errors in a sophisticated camera-type eye. Highlights[bullet] Crystallin protein knockdown induces central cataracts in an insect camera-type eye [bullet]Cataractous lenses project blurry images but have unchanged focal length [bullet]Resulting image degradation impacts behaviour in challenging low light conditions [bullet]Contrary to vertebrates, blurry vision does not affect refractive state

neuroscience↗

bioRxiv2024

A dynamin-like protein in the human malaria parasite plays an essential role in mitochondrial homeostasis and fission during asexual blood stages

Malaria parasite harbors a single mitochondrion and its proper segregation during the parasite multiplication is crucial for propagation of the parasite within the host. Mitochondrial fission machinery consists of a number of proteins that associate with mitochondrial membrane during segregation. Here, we have identified a dynamin-like protein in P. falciparum, PfDyn2, and deciphered its role in mitochondrial division, segregation and homeostasis. GFP targeting approach combined with high resolution microscopy studies showed that the PfDyn2 associates with mitochondrial membrane to form a clip/hairpin loop like structure around it at specific sites during mitochondrial division. The C-terminal degradation tag mediated inducible knock-down (iKD) of PfDyn2 resulted in significant inhibition of parasite growth. PfDyn2-iKD hindered mitochondrial development and functioning, decreased mtDNA replication, and induced mitochondrial oxidative-stress, ultimately causing parasite death. Further, treatment of parasites with dynamin specific inhibitors disrupted the recruitment of PfDyn2 on the mitochondria, blocked mitochondrial development, and induced oxidative stress. Regulated overexpression of a phosphorylation mutant of PfDyn2 (Ser-612-Ala) had no effect on the recruitment of PfDyn2 on the mitochondria; normal mitochondrial division and parasite growth showed that phosphorylation/dephosphorylation of this conserved serine residue (Ser612) may not be responsible for regulating recruitment of PfDyn2 to the mitochondrion. Overall, we show essential role of PfDyn2 in mitochondrial dynamics and fission as well as in maintaining its homeostasis during asexual cycle of the parasite.

cell biology↗

bioRxiv2023

Exploring the molecular makeup of support cells in insect camera eyes

Animals generally have either compound eyes, which have evolved repeatedly in different invertebrates, or camera eyes, which have evolved many times across the animal kingdom. Both eye types include two important kinds of cells: photoreceptor cells, which can be excited by light, and non-neuronal support cells (SupCs), which provide essential support to photoreceptors. Despite many examples of convergence in eye evolution, similarities in the gross developmental plan and molecular signatures have been discovered, even between phylogenetically distant and functionally different eye types. For this reason, a shared evolutionary origin has been considered for photoreceptors. In contrast, only a handful of studies, primarily on the compound eyes of Drosophila melanogaster, have demonstrated molecular similarities in SupCs. D. melanogaster SupCs (Semper cells and primary pigment cells) are specialized eye glia that share several molecular similarities with certain vertebrate eye glia, including Muller glia. This led us to speculate whether there are conserved molecular signatures of SupCs, even in functionally different eyes such as the image-forming larval camera eyes of the sunburst diving beetle Thermonectus marmoratus. To investigate this possibility, we used an in-depth comparative whole-tissue transcriptomics approach. Specifically, we dissected the larval principal camera eyes into SupC- and retina-containing regions and generated the respective transcriptomes. Our analysis revealed several conserved features of SupCs including enrichment of genes that are important for glial function (e.g. gap junction proteins such as innexin 3), glycogen production (glycogenin), and energy metabolism (glutamine synthetase 1 and 2). To evaluate the extent of conservation, we compared our transcriptomes with those of fly (Semper cells) and vertebrate (Muller glia) eye glia as well as respective retinas. T. marmoratus SupCs were found to have distinct genetic overlap with both fly and vertebrate eye glia. These results provide molecular evidence for the deep conservation of SupCs in addition to photoreceptor cells, raising essential questions about the evolutionary origin of eye-specific glia in animals.

neuroscience↗

bioRxiv2022

Probing the conserved roles of Cut in the development and function of optically different insect compound eyes.

Astonishing functional diversity exists among arthropod eyes, yet eye development relies on deeply conserved genes. This phenomenon is best understood for early events, whereas fewer investigations have focused on the influence of later transcriptional regulators on diverse eye organizations and the contribution of critical support cells, such as Semper cells (SCs). As SCs in Drosophila melanogaster secrete the lens and function as glia, they are critical components of ommatidia. Here, we perform RNAi-based knockdowns of the transcription factor cut (CUX in vertebrates), a marker of SCs, the function of which has remained untested in these cell types. To probe for the conserved roles of cut, we investigate two optically different compound eyes: the apposition optics of D. melanogaster and the superposition optics of the diving beetle Thermonectus marmoratus. In both cases, we find that multiple aspects of ocular formation are disrupted, including lens facet organization and optics as well as photoreceptor morphogenesis. Together, our findings highlight a generalized role for SCs in arthropod eye form and function and define Cut as a central player in mediating these functions.

developmental biology↗

bioRxiv2022

Evaluation of ERIC-PCR and MALDI-TOF as typing tools for multidrug resistant Klebsiella pneumoniae clinical isolates from a tertiary care center in India

Background and AimMultidrug resistant Klebsiella pneumoniae is associated with nosocomial infections in both outbreak and non-outbreak situations. The study intends to evaluate the potential of enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), a genomic based typing and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) proteomic-based typing techniques for clonal relatedness among multidrug resistant Klebsiella pneumoniae isolates. MethodologyMultidrug resistant clinical isolates of Klebsiella pneumoniae (n =137) were collected from March 2019 to February 2020. Identification and protein-based phylogenetic analysis were performed by MALDI-TOF MS. Genomic typing was done by ERIC-PCR and analyzed by an online data analysis service (PyElph). Dice method with unweighted pair group method with arithmetic mean (UPGMA) program was used to compare the ERIC profiles. The samples were also evaluated by PCR for the presence of genes encoding carbapenemases, extended spectrum beta lactamases (ESBLs) and mobile colistin resistance-1 (mcr1). Result and ConclusionIsolates were typed into 40 ERIC types, and six groups by MALDI-TOF-MS. PCR-based analysis revealed that all the strains harbored two or more ESBL and carbapenemase genes. None of the isolates revealed the presence of the plasmid mediated mcr-1 gene for colistin resistance. The study presents ERIC based typing as more robust in comparison to MALDI-TOF for finding the clonal relatedness in epidemiological studies.

microbiology↗

bioRxiv2022

Understanding the mechanism of Trikatu in type 2 diabetes mellitus and lipid-related metabolic disorders: A network pharmacology approach

ObjectiveTrikatu is an Indian polyherbal formulation comprising three herbs, i.e., Zingiber officinale, Piper longum, and Piper nigrum. It is traditionally used to treat metabolic disorders such as type 2 diabetes mellitus (T2DM), dyslipidemia, and obesity. However, its mechanism of action remains unknown. This study aims to explore the underlying therapeutic mechanism of Trikatu in T2DM and lipid metabolic disorders using network pharmacology (NP). MethodsTrikatu phytochemicals were retrieved from various databases and screened on the basis of druglikeness and oral bioavailability (>30%) score. Putative targets of the bioactive phytochemicals were identified using TargetNet, Similarity Ensemble Approach, and Swiss Target Prediction databases. Protein-protein interaction (PPI) network of overlapping targets of phytochemicals and metabolic disorders was constructed using NetworkAnalyst 3.0. The Bioactive Phytochemical-Target-Pathway (BP-T-P) network was constructed using cytoscape v3.8.2, and the key targets of Trikatu were analyzed by Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. ResultsTwenty bioactive phytochemicals and 102 targets of Trikatu were identified. PPI network and enrichment analysis showed that 51 targets of Trikatu phytochemicals such as RXRA, STAT3 and ESR1, GSK3B, TNF, NOS2/3 regulate pathways like insulin resistance, steroid hormone biosynthesis, regulation of lipolysis in adipocytes, adipocytokine & cGMP-PKG signalling pathways, arachidonic acid metabolism and bile secretion. The results were validated by molecular docking which showed that RXRA, STAT3 and ESR1 strongly interact with their ligands alpha gurjunene, beta-sitosterol, piperlongumine, genistein and E-beta carotene, respectively. ConclusionHence, the multiple target and multiple pathway approach of Trikatu can be further explored in pharmacokinetics / Pharmacodynamics studies.

bioinformatics↗

bioRxiv2022

Small-molecule inhibitors targeting prokaryotic ClpQ protease in Plasmodium display anti-malarial efficacies against blood and liver stages

The ATP-dependent ClpQY system is a prokaryotic proteasome-like machinery in the mitochondrion of malaria parasite, Plasmodium. This protease system is identified as a validated target for malaria intervention. Here we have identified drug-like small chemical compounds, pyrimidotriazine derivatives, as specific inhibitors of P. falciparum ClpQ (PfClpQ) having effective parasiticidal efficacies on asexual and liver stages. Screening of the Malaria Box compound library, using a robust in vitro activity assay, identified a hit compound targeting the PfClpQ protease with IC50 at ~750nM. Further, Structure-Activity Relationship (SAR) analysis, using a small library of derivatives of the hit compound, identified three potential lead compounds, ICGEB-L1, ICGEB-L2 and ICGEB-L3, which inhibited enzyme activity with IC50 in 100-200nM ranges. The three lead compounds effectively inhibited in vitro asexual stage parasite growth in similar concentration ranges with ~100-fold selectivity over mammalian cell line; in addition, these compounds effectively inhibited in vitro growth and maturation of hepatocytic stage parasites with EC50 in low nano-molar ranges. These compounds were found to effectively block the development of trophozoite stages to schizont stage, concurrently arresting development and segregation of parasite mitochondria, in asexual as well as hepatocytic stages of the parasite. These morphological and developmental effects of the drugs on parasites mimic the data from genetic ablation of PfClpQ. Importantly, all three compounds showed significant in vivo anti-parasitic efficacies on blood stages of P. berghei mouse malaria model. Overall these results suggest that these PfClpQ targeting compounds are promising candidates to develop new anti-malarials.

microbiology↗

bioRxiv2021

A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features

The recent release of SARS-CoV-2 genomic data from several countries has provided clues into the potential antigenic drift of the coronavirus population. In particular, the genomic instability observed in the spike protein necessitates immediate action and further exploration in the context of viralhost interactions. By temporally tracking 527,988 SARS-CoV-2 genomes, we identified invariant and hypervariable regions within the spike protein. We evaluated combination of mutations from SARS-CoV-2 lineages and found that maximum number of lineage-defining mutations were present in the N-terminal domain (NTD). Based on mutant 3D-structural models of known Variants of Concern (VOCs), we found that structural properties such as accessibility, secondary structural type, and intra-protein interactions at local mutation sites are greatly altered. Further, we observed significant differences between intra-protein networks of wild-type and Delta mutant, with the latter showing dense intra-protein contacts. Extensive molecular dynamics simulations of D614G mutant spike structure with hACE2 further revealed dynamic features with 47.7% of mutations mapping on flexible regions of spike protein. Thus, we propose that significant changes within spike protein structure have occurred that may impact SARS-CoV-2 pathogenesis, and repositioning of vaccine candidates is required to contain the spread of COVID-19 pathogen.

genomics↗

bioRxiv2020

Integrated genomic view of SARS-CoV-2 in India

India first detected SARS-CoV-2, causal agent of COVID-19 in late January-2020, imported from Wuhan, China. March-2020 onwards; importation of cases from rest of the countries followed by seeding of local transmission triggered further outbreaks in India. We used ARTIC protocol based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT from Oxford Nanopore Technology to understand introduction and local transmission. The analyses revealed multiple introductions of SARS-CoV-2 from Europe and Asia following local transmission. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, here, proposed as A4-clade based on its divergence within A-cluster. The viral haplotypes may link their persistence to geo-climatic conditions and host response. Despite the effectiveness of non-therapeutic interventions in India, multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.

microbiology↗