Biology subjects

Gujarati, S.

Publications and source records attributed to Gujarati, S..

3 recordsLinked to original sources

bioRxiv2025

Differential expression of mitochondria-associated genes in clinical samples of Plasmodium falciparum showing severe manifestations

The malaria parasite mitochondrial proteins are critical targets for antimalarial drugs, however, the emergence of drug resistance against the existing protein targets necessitates novel therapeutic approaches. In this study,we profiled mitochondrial sense and natural antisense transcripts (NATs) in 22 Plasmodium falciparum clinical isolates, classified into three disease groups - uncomplicated malaria (UNC, n=6), cerebral malaria (CM, n=4), and hepatic dysfunction (HD, n=12), using a custom, strand-aware 60K microarray, and validated the transcriptome using pooled, strand-specific RNA-seq (uncomplicated pool and complicated pool). Differential gene expression in the CM and HD cohort was obtained by comparing with uncomplicated malaria (UNC) as the control cohort. The analysis revealed distinct disease-specific sense and NATs, encoded by the mitochondrial genome, along with those encoded in the nucleus and targeted to the parasite mitochondria. Although mitochondrial activity is known to be reduced in blood-stage malaria, upregulation of genes linked to tricarboxylic-acid-cycle and electron-transport in the CM cluster indicates disrupted mitochondrial bioenergetics in severe disease. Profiling of sense and antisense mitochondrial transcripts reveal a correlated expression of sense-antisense transcript pairs in both the disease manifestations, indicating a potential regulatory role of NATs in mitochondrial function. These data provide direct evidence of NATs originating from the parasite mitochondrial genome and nominate key NATs against core mitochondrial functions as potential non-conventional antimalarial targets.

genomics↗

bioRxiv2023

A Tale of Two Parasites: A Glimpse into the clinical RNA Methylome of P. falciparum and P. vivax isolates

BackgroundUnderstanding the molecular mechanisms of the malarial parasites in hosts is crucial for developing effective treatments. Epitranscriptomic research on pathogens has unveiled the significance of RNA methylation in gene regulation and pathogenesis. We present the first report investigating methylation signatures and alternative splicing events using Nanopore Direct RNA Sequencing to single-base resolution in Plasmodium falciparum and P. vivax clinical isolates with hepatic dysfunction complications. MethodologyWe performed direct RNA Sequencing using Nanopore from clinical isolates of P. falciparum and P. vivax showing hepatic dysfunction manifestation. Subsequently we performed transcriptome reconstruction using FLAIR and transcript classification using SQANTI3 followed by methylation detection using CHEUI and m6Anet to identify N6-methyladenosine (m6A) and 5-methylcytosine (m5C) methylation signatures. We also documented alternative splicing events from both the datasets. ResultsThe reference genome of Plasmodium reports >5000 genes out of which we have identified [~]50% as expressed in the two sequenced isolates, including novel isoforms and intergenic transcripts, highlighting extensive transcriptome diversity. The distinct RNA methylation profiles of m6A and m5C from the expressed transcripts were observed in sense, Natural Antisense Transcripts (NATs) and intergenic categories hinting at species-specific regulatory mechanisms. Modified transcripts originating from apicoplast and mitochondrial genomes have also been detected. These modifications are unevenly present in the annotated regions of the mRNA, potentially influencing mRNA export and translation. We have observed several splicing events, with alternative 3and 5end splicing predominating in our datasets suggesting differences in translational kinetics and possible protein characteristics in these disease conditions. ConclusionIn our data we are showing the presence of modified sense, NATs and alternatively spliced transcripts. These phenomena together suggest the presence of multiple regulatory layers which decides the post-translational proteome of the parasites in particular disease conditions. Studies like these will help to decipher the post-translational environments of malaria parasites in vivo and elucidate their inherent proteome plasticity, thus allowing the conceptualization of novel strategies for interventions.

genomics↗

bioRxiv2019

Description of Klebsiella indica sp. nov., isolated from the surface of tomato.

A novel bacterial strain designated TOUT106T was isolated from the surface of a tomato collected from the local vegetable market in Pune, India. The cells were rod shaped, Gram-stain-negative, encapsulated and non-motile. The strain TOUT106T grows as mucoid and translucent colonies on blood agar medium and the best growth was observed at 28{degrees}C and at pH 7.0, and could tolerate up to 2% (w/v) NaCl. On the basis of 16S rRNA gene sequence analysis, strain TOUT106T was placed under Salmonella clade, with close similarity to Salmonella enterica subsp. arizonae strain NCTC 8297T (98.42%). Genome-based phylogenetic analysis revealed that the strain forms a distinct branch within the Klebsiella clade and K. michiganensis DSM25444T and K. oxytoca NBRC105695T were the closest neighbor. The genomic DNA G+C content of strain TOUT106T was 53.53 mol%. The average nucleotide identity of TOUT106T was less 86.4% with closely related members of the family Enterobacteriaceae. The major fatty acids of strain TOUT106T were C16:0, C17:0 cyclo, C14:0 3OH/C16:1 iso, C14:0, C19:0 cyclo w8c, C18:1 w6c/C18:1 w7c, C12:0 and C16:1 w7c/C16:1 w6c. The strain TOUT106T showed differences in physiological, phenotypic and protein profiles by MALDI-TOF MS to its closest relatives. Based on the phenotypic including chemotaxonomic properties and phylogenetic analysis the strain TOUT106T could be distinguished from the recognized species of the genus Klebsiella, was suggested to represent a novel species of this genus, for which the name Klebsiella indica sp. nov. is proposed. The type strain is TOUT106T (=MCC 2901T).

microbiology↗