Biology subjects

Khairnar, S. V.

Publications and source records attributed to Khairnar, S. V..

3 recordsLinked to original sources

bioRxiv2025

Enhanced respiratory electron dissipation promotes mycobacterial biofilm longevity

Mycobacterium tuberculosis organizes as multicellular structures like granuloma and biofilm within human lungs and these lifestyles are critical for the pathophysiological outcomes. Granuloma has been the hallmark of M. tuberculosis infection and has been studied extensively. However, the metabolic interplay dictating biofilm development remains poorly understood. We show that supplementation of immunometabolites, nitrate or fumarate, extends mycobacterial biofilm lifespan dramatically. This longevity is enabled by suppression of dormancy regulons and maintenance of active metabolic state. These results establish that access to alternative electron acceptors directly influences mycobacterial biofilm fate. By linking dormancy suppression to prolonged structural integrity, our study identifies respiratory flexibility as a determinant of mycobacterial biofilm persistence. These findings reveal a central metabolic lever that dictates biofilm survival and open new avenues for targeting mycobacterial biofilms in clinical settings.

microbiology↗

bioRxiv2025

Aerobicity stimulon in Escherichia coli revealed using multi-scale computational systems biology of adapted respiratory variants

Energy homeostasis facilitated by the interplay of substrate-level and oxidative phosphorylation is crucial for bacterial adaptation to diverse substrates and environments. To investigate how bioenergetic systems optimize under restrictive conditions, we evolved ETS variants with distinct proton-pumping efficiencies (1, 2, 3, or 4 proton(s) per electron) on succinate and glycerol. These substrates impose unique metabolic constraints: succinate requires complete gluconeogenesis, while glycerol supports mixed glycolytic and gluconeogenic fluxes. Multi-scale computational analysis of the strains revealed (a) Growth optimization across carbon substrates for multiple ETS variants, (b) A conserved aerobicity stimulon comprising seven independently regulated gene groups that are co-regulated with increasing aerobic capacities, (c) Proteome reallocation linked to aerobicity, validated using genome-scale metabolism and expression modeling, and (d) Carbon source-specific compensatory mutations in succinate transporters and regulatory elements. These findings define the aerobicity stimulon and establish a unifying framework for understanding bacterial respiratory flexibility, demonstrating how transcriptional networks and metabolic systems integrate to achieve energy homeostasis and bioenergetic resilience.

systems biology↗

bioRxiv2025

Hidden Markov Model-Based Prokaryotic Genome Space Mining Reveals the Widespread Pervasiveness of Complex I and Its Potential Evolutionary Scheme

Most cellular reactions are interdependent; however, a subset of reactions often associates more closely to form a defined reaction pathway. An extreme arrangement of interdependent reactions occurs when the cognate proteins physically associate to constitute a complex. Respiratory complex I is one of the largest membrane resident protein assemblies. Besides being the hallmark of bioenergetics, this enzyme complex is critical for redox homeostasis and transport. The evolutionary scheme for the development of this enzyme complex is poorly understood due to associated challenges like complications in delineating close homologs and diverse subunit ancestry. We used custom Hidden Markov Model profiles to examine the available prokaryotic genome space to trace the distribution pattern of fourteen core Nuo subunits of Complex I. We report: (a) a sensitive HMMER-based workflow for comprehensively annotating and analyzing the Nuo subunits, which can be adapted to multiple such analyses; (b) the first curated species-level distribution of Nuo subunits; (c) multiple variants of Complex I across [~]11,000 species with 51.2% species having complete complex; (d) presence of Complex I variants on plasmids which potentially facilitated the evolutionary distribution; (e) extension of our workflow for examining distribution of mitochondrial Complex I accessory subunits among prokaryotes highlighting their evolutionary roots. We have also developed a web application to facilitate the convenient dissemination of our compiled resources. The knowledge of bioenergetic repertoire is critical in the successful targeting of energy metabolism for antimicrobial development.

microbiology↗