Biology subjects

Satyam, R.

Publications and source records attributed to Satyam, R..

4 recordsLinked to original sources

bioRxiv2026

Malaria parasites coordinate host cell remodeling through the AP2-HCR DNA-binding protein

Parasite-induced host cell remodeling is essential for Plasmodium falciparum survival during the intraerythrocytic developmental cycle (IDC), yet the transcriptional mechanisms coordinating this process remain poorly understood. Here, we characterize an essential ApiAP2 transcription factor, PfAP2-HCR (host cell remodeling), during both the asexual and sexual blood stages of P. falciparum. Conditional truncation of pfap2-hcr demonstrated that PfAP2-HCR is essential for ring stage development and parasite maturation. Loss of PfAP2-HCR disrupted the expression of host cell remodeling genes, resulting in the absence of Maurers clefts and collapse of the parasite protein export machinery. Integrated RNA-seq and ChIP-seq analyses revealed that PfAP2-HCR directly or indirectly regulates approximately 30% of exported proteins, including 27 essential exported factors, the parasitophorous vacuole membrane (PVM) resident protein EXP1, and the core PTEX component EXP2. We further show that PfAP2-HCR is also indispensable for gametocytogenesis, as conditional truncation results in either complete ablation or the formation of severely deformed gametocytes. Together, these findings establish PfAP2-HCR as a central transcriptional regulator that orchestrates the expression of host cell remodeling factors required to transform a terminally differentiated erythrocyte into a permissive environment for parasite survival, development, and transmission.

microbiology↗

bioRxiv2025

plasmoRUtils: A one-stop R Package for Plasmodium and other Apicomplexan parasite-related Bioinformatics analysis

Bioinformatics analysis of non-model organisms remains challenging due to the limited availability of specialized tools, as most R packages are optimized for well-annotated model species. This problem is exacerbated by genomic and proteomic data being scattered across multiple databases, each employing different identifiers based on varying reference annotations. Comprehensive databases have been developed to disseminate knowledge related to Apicomplexan genomics and proteomics, such as VEupathDB. Several specialised databases, particularly for the malaria parasite Plasmodium, have been developed such as ApicoTFDB, malaria.tools, MPMP, MIIP, Phenoplasm, PlasmoBase, alongside broader resources like HitPredict and TED. However, these platforms often suffer from manual query interfaces, outdated identifiers, and inefficient data retrieval methods, complicating their use for large-scale bioinformatic analyses. To address these limitations, we present plasmoRUtils, an R package designed to streamline database access and data harmonization for Apicomplexan research. plasmoRUtils enables the retrieval of data tables using single-line R functions and standardized Ensembl gene IDs as input. Thanks to the APIs available for some databases such as VEuPathDB, the package also provides functions to build CLI-based queries for VEuPathDBs component databases. Additional support includes performing overrepresentation analyses and estimating parasite transcriptomic age/stage using single-cell or bulk RNA-Seq references. By automating data retrieval and transformation within RStudio, plasmoRUtils eliminates the need for manual database queries, facilitating end-to-end workflow development without leaving the R environment. Available on GitHub https://github.com/Rohit-Satyam/plasmoRUtils, with comprehensive documentation, plasmoRUtils represents a critical step toward efficient and reproducible bioinformatics for Apicomplexan research.

bioinformatics↗

bioRxiv2023

PfAP2-MRP DNA-binding protein is a master regulator of parasite pathogenesis during malaria parasite blood stages

Malaria pathogenicity results from the parasites ability to invade, multiply within and then egress from the host red blood cell (RBC). Infected RBCs are remodeled, expressing antigenic variant proteins (such as PfEMP1, coded by the var gene family) for immune evasion and survival. These processes require the concerted actions of many proteins, but the molecular regulation is poorly understood. We have characterized an essential Plasmodium specific Apicomplexan AP2 (ApiAP2) transcription factor in Plasmodium falciparum (PfAP2-MRP; Master Regulator of Pathogenesis) during the intraerythrocytic developmental cycle (IDC). An inducible gene knockout approach showed that PfAP2-MRP is essential for development during the trophozoite stage, and critical for var gene regulation, merozoite development and parasite egress. ChIP-seq experiments performed at 16 hour post invasion (h.p.i.) and 40 h.p.i. matching the two peaks of PfAP2-MRP expression, demonstrate binding of PfAP2-MRP to the promoters of genes controlling trophozoite development and host cell remodeling at 16 h.p.i. and antigenic variation and pathogenicity at 40 h.p.i. Using single-cell RNA-seq and fluorescence-activated cell sorting, we show de-repression of most var genes in{Delta} pfap2-mrp parasites that express multiple PfEMP1 proteins on the surface of infected RBCs. In addition, the{Delta} pfap2-mrp parasites overexpress several early gametocyte marker genes at both 16 and 40 h.p.i., indicating a regulatory role in the sexual stage conversion. Using the Chromosomes Conformation Capture experiment (Hi-C), we demonstrate that deletion of PfAP2-MRP results in significant reduction of both intra-chromosomal and inter-chromosomal interactions in heterochromatin clusters. We conclude that PfAP2-MRP is a vital upstream transcriptional regulator controlling essential processes in two distinct developmental stages during the IDC that include parasite growth, chromatin structure and var gene expression.

genomics↗

bioRxiv2019

Towards a Chimeric Vaccine against Multiple Isolates of Mycobacteroides - An Integrative Approach

Nontuberculous mycobacterial infection (NTM) such as endophthalmitis, dacryocystitis, canaliculitis are pervasive across the globe and are currently managed by antibiotics such as cefoxitin/imipenem and azithromycin/clarithromycin. However, the recent cases of Mycobacteroides developing drug resistance reported along with the improper practice of medicine intrigued us to explore its genomic and proteomic canvas at a global scale. A timely developed vaccine against Mycobacteroides is, therefore, a much requirement. Consequently, we carried out a vivid Genomic study on five recently sequenced strains of Mycobacteroides and explored their Pan-Core genome/ proteome. The promiscuous antigenic proteins were identified via a subtractive proteomics approach that qualified for virulence causation, resistance and essentiality factors for this notorious bacterium. An integrated pipeline was developed for the identification of B Cell, MHC class I, II epitopes. Our final vaccine construct, V6 qualified for all tests such as absence for allergenicity, presence of antigenicity, etc. and contains {beta} defensin adjuvant, linkers, LAMP1 signal peptide, and PADRE (Pan HLA-DR epitopes) amino acid sequence. The vaccine construct, V6 also interacts with a maximum number of MHC molecules, and the TLR4/MD2 complex confirmed by docking and molecular dynamics simulation studies. The knowledge harnessed from the current study can help improve the current treatment regimens and propel further related studies.

bioinformatics↗