Biology subjects

Bahadur, R.

Publications and source records attributed to Bahadur, R..

3 recordsLinked to original sources

bioRxiv2026

Gene regulatory co-expression networks decipher potential lncRNA-miRNA-mRNA interactions modulating transcription regulation in neurodegeneration

Neurodegenerative diseases are complex disorders characterised by progressive neuronal loss and widespread transcriptomic dysregulation; however, the coordinated interactions among coding and non-coding RNAs that contribute to disease progression remain incompletely understood. In this study, RNA-seq datasets from disease-relevant neuronal populations and brain regions representing Alzheimers disease (AD), Parkinsons disease (PD) and amyotrophic lateral sclerosis (ALS) were analysed using an integrative network-based framework. Differential expression analysis coupled with weighted gene co-expression network analysis identified modules significantly correlated with disease and prioritised highly connected hub genes. Integration of these hub genes with curated RNA interaction database enabled the construction of candidate lncRNA-miRNA-mRNA regulatory networks. Functional enrichment analysis revealed Gene Ontology biological processes associated with synaptic signalling, mitochondrial function, RNA metabolism and neuroinflammatory responses across neurodegenerative conditions. The inferred regulatory networks suggested both disease-specific and shared post-transcriptional regulatory modules involving key hub genes and non-coding RNAs. Additionally, putative sequence variants were identified within untranslated regions of selected hub genes, suggesting potential alterations in miRNA-mediated regulations. Therefore, this study provides a systems-level view of transcriptomic dysregulation across major neurodegenerative diseases and identifies candidate regulatory interactions and molecular targets for future functional investigation.

bioinformatics↗

bioRxiv2026

Rhizobial enzyme reveals pH-driven catalytic switching and ʟ-amino acid incorporation by ʟ,-transpeptidases

Nearly all bacteria are surrounded by a mesh-like macromolecule called peptidoglycan that gives them their shape and helps them resist turgor pressure. To grow and maintain their peptidoglycan, bacteria produce a wide range of enzymes, including the relatively understudied ,[x1D05]-transpeptidase (LDT) family. LDTs can catalyse several different reactions and vary widely in copy number: some bacteria have none, whilst others have more than twenty. To better understand why some bacteria have so many LDTs, we examined 18 putative ones from Rhizobium johnstonii, a nitrogen-fixing, symbiotic bacterium. Heterologous expression revealed several highly active enzymes, one of which, LdtRj8, we further characterized in detail. In vitro assays showed that LdtRj8 was capable of ,[x1D05]-transpeptidation, carboxypeptidation, substitution, and endopeptidation, but that its preferred activity differed at different pHs. LdtRj8 particularly excelled at ,[x1D05]-substitution, utilizing all of the tested [x1D05]-amino acids, and, surprisingly, most of the -amino acids as well. LdtRj8's pH-modulated activity could help R. johnstonii respond to acidic conditions encountered throughout the rhizobium-legume symbiosis, and its -amino acid substitution activity, which we show to be a more general property of LDTs, may regulate ,[x1D05]-transpeptidation and explain the existence of isomeric muropeptides often reported in the literature.

biochemistry↗

bioRxiv2021

Cleavage of Braun lipoprotein Lpp from the bacterial peptidoglycan by a paralog of L,D-transpeptidases, LdtF

Gram-negative bacterial cell envelope is made up of an outer membrane (OM), an inner membrane (IM) that surrounds the cytoplasm, and a periplasmic space between the two membranes containing peptidoglycan (PG or murein). PG is an elastic polymer that forms a mesh-like sacculus around the IM protecting cells from turgor and environmental stress conditions. In several bacteria including E. coli, the OM is tethered to PG by an abundant OM lipoprotein, Lpp (or Braun lipoprotein) that functions to maintain the structural and functional integrity of the cell envelope. Since its discovery Lpp has been studied extensively and although L,D-transpeptidases, the enzymes that catalyse the formation of PG-Lpp linkages have been earlier identified, it is not known how these linkages are modulated. Here, using genetic and biochemical approaches, we show that LdtF (formerly yafK), a newly-identified paralog of L,D-transpeptidases in E. coli is a murein hydrolytic enzyme that catalyses cleavage of Lpp from the PG sacculus. LdtF also exhibits glycine-specific carboxypeptidase activity on muropeptides containing a terminal glycine residue. LdtF is earlier presumed to be an L,D-transpeptidase; however, our results show that it is indeed an L,D-endopeptidase that hydrolyses the products generated by the L,D-transpeptidases. To summarize, this study describes the discovery of a murein endopeptidase with a hitherto unknown catalytic specificity that removes the PG-Lpp cross-links suggesting a role for LdtF in regulation of PG-OM linkages to maintain the structural integrity of the bacterial cell envelope. Significance statementBacterial cell walls contain a unique protective exoskeleton, peptidoglycan, which is a target of several clinically important antimicrobials. In Gram-negative bacteria, peptidoglycan is covered by an additional lipid layer, outer membrane that serves as permeability barrier against entry of toxic molecules. In some bacteria, an extremely abundant lipoprotein, Lpp staples outer membrane to peptidoglycan to maintain the structural integrity of the cell envelope. In this study, we identify a previously unknown peptidoglycan hydrolytic enzyme that cleaves Lpp from the peptidoglycan sacculus and show how the outer membrane-peptidoglycan linkages are modulated in Escherichia coli. Overall, this study helps in understanding the fundamental bacterial cell wall biology and in identification of alternate drug targets for development of new antimicrobials.

microbiology↗