Biology subjects

Rana, R.

Publications and source records attributed to Rana, R..

10 recordsLinked to original sources

bioRxiv2025

Pseudomonas aeruginosa SPT08, a tomato endophyte, improves plant growth and controls bacterial wilt in tomato

Endophytes are a class of non-pathogenic microorganisms that reside within a plant and contribute to their health. Here, we isolated several endophytes from cotyledon-stage tomato seedlings that inhibited the growth of Ralstonia pseudosolanacearum, the bacterial wilt pathogen of tomato. One such endophyte, Pseudomonas aeruginosa SPT08, protected tomato seedlings as well as grown-up plants from the wilt disease. SPT08 also improved the tomato plant height by 20% and root growth by 60% in weight. SPT08 colonization inside tomato seedlings as well as in grown-up plants was studied using green fluorescent protein to demonstrate its endophytic behavior. SPT08 exhibited twitching and swimming motility and produced extracellular enzymes such as pectinase, protease, and amylase. SPT08 tested positive for several plant growth-promoting features such as phosphate solubilization, production of siderophore, plant hormone auxin, hydrogen cyanide, and ammonia. These features were further corroborated with SPT08 whole genome sequence. SPT08 genome is 6265489 bp, with 66.59% G+C and 5786 coding genes, including type II, III, and VI protein secretion systems. The antiSMASH tool identified potential for several secondary metabolites, including antibiotics, in SPT08. This study underscores the utility of P. aeruginosa SPT08 bio-protection from bacterial wilt and growth promotion agent in tomato. HighlightsPseudomonas aeruginosa SPT08, an endophyte isolated from tomato seedlings that inhibits bacterial wilt pathogen R. pseudosolanacearum, can control bacterial wilt in tomato plants and enhance the height and root growth.

plant biology↗

bioRxiv2025

Circulating Biomarkers for Therapeutic Response to Immune Checkpoint Inhibitor Therapy in Patients with Advanced Lung Cancer

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in the treatment of advanced lung cancer (ALC), but not all patients benefit. To identify responders, patient selection, categorization, and the identification of specific predictive biomarkers are crucial. Our research aims to identify circulating metabolites that could be used to stratify patients into potential responders prior to the initiation of ICIs and to monitor clinical response in real-time during treatment. In the discovery phase, plasma samples (n = 25) from ALC patients receiving ICIs were analyzed using unbiased metabolomics and validated in a distinct patient cohort (n = 39). Five potential biomarkers were identified (FC > 1.5, p 0.05, AUC 0.81-1), including Thiourea and a combined metabolite panel (CMP) consisting of sphingosine-1-phosphate, gentisic acid, glutathione, and 4-hydroxybutanone. Early on-treatment high plasma levels of Thiourea were significantly associated with 5-year progression-free survival [Hazard ratio (HR) = 0.038, 95% confidence interval (CI) = 0.013-0.107, p<0.001] and overall survival [HR = 0.048, 95% CI = 0.019-0.120, p<0.001]. Low levels of CMP early on treatment were significantly associated with progression-free survival [HR = 8.119, 95% CI: 3.767-17.501, p<0.001] and overall survival [HR = 7.367, 95% CI: 3.517-15.433, 3.517-15.433, p<0.001]. This predictive plasma metabolite panel could serve as promising circulating biomarkers for predicting the therapeutic response of ICIs in ALC patients.

cancer biology↗

bioRxiv2024

Xanthomonas protegens sp. nov., a rice seed-associated probiotic and taxonomic outlier species of Xanthomonas sontii

Rice seed microbiota play a vital role throughout their growth and developmental stages. Xanthomonas sontii is known as an abundant, core-vertically transmitted rice seed endophyte with probiotic properties. Studies reveal a less explored world of non-pathogenic Xanthomonas (NPX) species like X. sontii and X. indica that are associated with healthy rice seeds. The present study reports the isolation, biochemical characterization, and in-depth taxonogenomic evidence for a third NPX species, X. protegens, from rice seeds, a taxonomic outlier of X. sontii. It also highlights the importance of using multiple taxonogenomic indices to identify taxonomic outlier species. Similar to the other two NPX species, the new member species is also non-pathogenic and provides in vivo protection to rice plants from Xanthomonas oryzae pv. oryzae upon leaf clip inoculation. The pangenome investigation suggested a set of unique genes to the novel species that might be important in adaptation to rice plants and differentiate it from other NPX species. The study will allow the design of markers for the identification of these NPX members, targeted culturomics of a particular NPX species and in the discovery of other novel NPX species from healthy rice seed microbiome for further exploitation in rice health.

evolutionary biology↗

bioRxiv2023

Xanthomonas sontii, and not Xanthomonas sacchari, is the dominant, vertically transmitted core rice seed endophyte

Seeds endophytes, particularly the abundant, core and vertically transmitted species, are major areas of focus in the host microbiome studies. Apart from being the first members to colonize, they accompany the plant throughout its development stages and also to the next generation. In a recently published study from china, a Xanthomonas species was reported as the keystone species that is core endophyte and vertically transmitted in rice with probiotic properties. However, the species status was wrongly reported as X. sacchari. Such report is misleading as Xanthomonas sacchari is a well-known and pathogenic species of sugarcane, and the study did not include the two-probiotic non-pathogenic Xanthomonas species from rice seeds, Xanthomonas sontii and Xanthomonas indica, that were discovered and investigated in details by our group, leading to the wrong inference. By including these species, we have correctly established the phylogenetic and taxonomic identity of keystone species as Xanthomonas sontii, a non-pathogen with plant protective functions. The course correction will enable researchers to use the correct reference or lab strain of X. sontii for further fundamental studies and translational research towards future agriculture.

microbiology↗

bioRxiv2023

Luteibacter sahnii sp. nov., a novel yellow-pigmented probiotic bacterium from rice seed microbiome.

The genus Luteibacter, a member of the family Rhodanobacteraceae, encompasses Gram-negative bacteria found in diverse environments. In the present study, four yellow-pigmented bacterial isolates designated as PPL193T, PPL201, PPL552, and PPL554 were obtained and identified as Gram-negative, rod-shaped, and motile bacteria. Biochemical characterization and examination of the 16S rRNA gene sequence, derived from the genomic sequence, identified it as belonging to the genus Luteibacter. The isolates are closely related to Luteibacter yeojuensis R2A16-10T, forming a distinct monophyletic lineage with L. aegosomatis KCTC 92392T and L. anthropi CCUG25036T. The calculated values for pairwise ortho Average Nucleotide Identity and digital DNA-DNA hybridization in comparison to previously reported Luteibacter species fell below the established thresholds for species delineation. As this novel species was isolated from rice seeds as a potential Xanthomonas due to its distinctive yellow-colored colonies, we sought to identify the presence of xanthomonadin pigment in this species. Intriguingly, our findings revealed the presence of the typical peak corresponding to xanthomonadin in the UV spectra, confirming its presence in this novel species and adaptation to plant habitat. Furthermore, the detailed genomic investigation also uncovered the genomic locus corresponding to xanthomonadin biosynthetic gene cluster, further suggesting that members of this novel species are co-habitants of plant pathogenic and plant probiotic Xanthomonas group of phytobacteria within rice seeds. Apart from protease production, the species was found to produce Indole-3-Acetic Acid (IAA) in higher quantities and was also able to protect plants from Xanthomonas oryzae pv. oryzae, a major pathogen of rice indicating its probiotic nature. Genome scanning revealed the presence of genomic region(s) encoding loci for biosynthesis of anti-microbial peptides and other metabolites with probiotic properties, further confirming its probiotic properties. This study highlights the importance of using a combination of phenotypic and genotypic methods for bacterial identification and expands our knowledge of the diversity and distribution of diverse bacteria associated with rice seeds and their microbiome. Luteibacter sahnii sp. nov. is proposed as a novel species of the genus Luteibacter with PPL193T=MTCC 13290T=ICMP 24807T=CFBP 9144T as its type strain and PPL201, PPL552, and PPL554 as other constituent members.

microbiology↗

bioRxiv2023

Comparative genomics-based insights into diversification and bio-protection function of Xanthomonas indica, a non-pathogenic species of rice

Xanthomonas species have been extensively studied as major and model pathogens of plants. However, there is an increasing recognition of the complex and large world of non-pathogenic species of Xanthomonas in the recent decades. One pathogenic Xanthomonas species has been known in rice for the last hundred years, yet in recent years, three non-pathogenic Xanthomonas (NPX) species have been reported. Thus, there is a need to understand the species-level diversity of NPXs like their pathogenic counterparts. In the present study, we report isolation and investigation into the genomic diversity of Xanthomonas indica, a newly discovered NPX species from rice. The study allowed us to establish the relationship of X. indica strains within clade I of Xanthomonads. All the strains formed a distinct but diverse clade compared to clades corresponding to other NPX species from rice and other hosts. X. indica lacks major virulence factors found in their pathogenic counterparts. Identification of highly diverse strains and open-pan genome indicates ongoing selection to acquire new functions for adaptation. X. indica also harbours large-scale interstrain variations in the lipopolysaccharide O-antigen biosynthetic gene cluster, which hints at the selection at this locus. Interestingly, all the diverse strains of X. indica were able to protect rice from bacterial leaf blight pathogen of rice upon leaf clip inoculation. Comparative genomics revealed the association of a RiPP, a metalloprotease and a bacterial-killing type IV secretion system conserved across its related member species, including X. sontii, in the clade I with in-vivo anti-pathogenic properties. Overall the study has provided novel evolutionary insights into an important NPX member species. The findings and genomic resources will allow further systematic molecular studies to understand its interaction with the host plant.

genomics↗

bioRxiv2022

Xanthomonas indica sp. nov., a non-pathogenic bacterium isolated from healthy rice (Oryza sativa) seeds from India

Two yellow pigmented bacterial strains were isolated from healthy rice seeds. The strains designated as PPL560T and PPL568 were identified as members of genus Xanthomonas based on analysis of biochemical and 16S rRNA gene sequence retrieved from whole genome sequence. Isolates formed a distinct monophyletic lineage with X. sontii and X. sacchari as the closest relatives in the phylogenetic tree based on core gene content shared by reported species in genus Xanthomonas. Pairwise ortho Average Nucleotide Identity and digital DNA-DNA hybridisation values calculated against other species of Xanthomonas were below their respective cut-offs. In planta studies revealed that PPL560T and PPL568 are non-pathogenic to rice plants upon leaf clip inoculation. Absence of type III secretion system related genes and effectors further supported their non-pathogenic status. Herein, we propose Xanthomonas indica sp. nov. as novel species of genus Xanthomonas with PPL560T=MTCC13185 as its type strain and PPL568 as another constituent member.

evolutionary biology↗

bioRxiv2021

Reversal of the renal hyperglycemic memory by targeting sustained tubular p21 expression

A major therapeutic obstacle in diabetes mellitus is the metabolic or hyperglycemic memory: the persistence of impaired organ function despite improvement of blood glucose. Therapies reversing the hyperglycemic memory and thus improving already established organ-dysfunction are lacking, but urgently needed considering the increasing prevalence of diabetes mellitus worldwide. Here we show that glucose-mediated changes in gene expression largely persist in diabetic kidney disease (DKD) despite reversing hyperglycemia. The senescence-associated cyclin-dependent kinase inhibitor p21 (Cdkn1a) was the top hit among genes persistently induced by hyperglycemia and was associated with sustained induction of the p53-p21 pathway. Persistent p21 induction was confirmed in various animal models, in several independent human samples and in in vitro models. Tubular p21 expression and urinary p21-levels were associated with DKD severity and remained elevated despite improved blood glucose levels in humans, suggesting that p21 may be a biomarker indicating persistent ("memorized") kidney damage. Glucose-mediated p21 induction and tubular senescence were enhanced in mice with reduced levels of the disease resolving protease activated protein C (aPC). Mechanistically, glucose-induced and sustained tubular p21 expression is linked with demethylation of its promoter and reduced DNMT1 expression. aPC reverses already established p21 expression independent of its anticoagulant function through receptor signaling. Accordingly, new pharmacological approaches specifically mimicking aPC signaling (3K3A-aPC, parmodulin-2) enabled the reversal of glucose-mediated sustained tubular p21 expression, tubular senescence, and DKD. Thus, p21-dependent tubular senescence contributes to the hyperglycemic memory but can be therapeutically targeted. Single sentence summaryaPC signaling targets persistent p21 expression and tubular senescence and reverses the hyperglycemic memory in diabetic kidney disease.

molecular biology↗

bioRxiv2020

Discerning role of a functional arsenic resistance cassette in evolution and adaptation of a rice pathogen

Arsenic (As) is highly toxic element to all forms of life and is a major environmental contaminant. Understanding acquisition, detoxification, and adaptation mechanisms in bacteria that are associated with host in arsenic-rich conditions can provide novel insights into dynamics of host-microbe-microenvironment interactions. In the present study, we have investigated an arsenic resistance mechanism acquired during the evolution of a particular lineage in the population of Xanthomonas oryzae pv. oryzae (Xoo), which is a serious plant pathogen infecting rice. Our study revealed the horizontal acquisition of a novel chromosomal 12kb ars cassette in Xoo IXO1088 that confers high resistance to arsenate/arsenite. The ars cassette comprises several genes that constitute an operon induced in the presence of arsenate/arsenite. Transfer of cloned ars cassette to Xoo BXO512 lacking it confers arsenic resistance phenotype. Further, the transcriptional response of Xoo IXO1088 under arsenate/arsenite exposure was analyzed using RNA sequencing. Arsenic detoxification and efflux, oxidative stress, iron acquisition/storage, and damage repair are the main cellular responses to arsenic exposure. Our investigation has provided novel insights in to how a pathogenic bacterium is coping with arsenic-rich unique micro-environments like seen in rice growing in submerged water conditions. Impact statementArsenic accumulation in rice is a serious and unique agronomic issue. Arsenic contaminated groundwater used for irrigation purposes is adding to the accumulation of arsenic in rice. Submerged conditions in the paddy fields further induce the prevalence of toxic inorganic arsenic species in the environment. Our genomics and transcriptomics-based study reveals how a rice pathogen is coping with the lethal concentrations of arsenic by acquiring a novel resistance cassette during diversification into lineages. Acquisition of such detoxification mechanisms can provide a selective advantage to the bacterial population in avoiding toxicity or enhancing virulence and to their on-going evolutionary events. While there are numerous studies on plant-pathogen-environment interactions, our study highlights the importance of systematic studies on the role of unique micro-environmental conditions on the evolution of host-adapted pathogens/microbes.

microbiology↗

bioRxiv2020

Cannabidiol Interactions with Voltage-Gated Sodium Channels

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, showing CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies illuminate why the closely-related psychoactive compound THC may not bind to these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD with sodium channels.

biophysics↗