Biology subjects

Taneja, B.

Publications and source records attributed to Taneja, B..

5 recordsLinked to original sources

bioRxiv2026

Tracking vaginal microbiome transitions in bacterial vaginosis for cues of antibiotic resilience

BackgroundBacterial vaginosis (BV) is a common and difficult-to-treat vaginal disorder, with significant implications for reproductive health, particularly in low and middle-income countries. Clinical cure based on symptom resolution or Nugent scores often do not correspond to restoration of healthy vaginal microbiome. Factors underlying treatment failure remain poorly defined, warranting the need for understanding post-treatment microbiome dynamics to improve long-term outcomes. ObjectivesTo delineate longitudinal vaginal bacteriome dynamics, integrating microbial composition, transition patterns, and clinical symptoms in a closely followed cohort of women with BV based on treatment outcome. MethodsVaginal swabs from reproductive-age women (18-45 years) were collected and classified as BV-positive ([≥]7) or healthy ([≤]3) using Nugent scoring. BV cases were treated using single-dose secnidazole and followed for three months. Sociodemographic, clinical, and behavioral data were statistically analyzed across groups. Vaginal microbiome composition was assessed using 16S rRNA sequencing, evaluating taxonomic profiles, alpha and beta diversity, differential abundance, and co-occurrence networks. ResultsAntibiotic treatment reduced overall microbial diversity and shifted community composition toward healthy controls, though relapse samples retained higher diversity of BV-associated taxa such as Sneathia, Dialister, and Gardnerella, while no-relapse and control groups showed higher Lactobacillus abundance. Corynebacterium amycolatum appeared protective, while Mycoplasma and Fusobacterium played symptom-specific roles. Microbial network analysis showed denser and more persistent associations in baseline and relapse groups, with Sneathia remaining a central node. ConclusionShort-term symptom resolution in BV does not correspond to full microbial recovery; necessary for long-term remission. Functional traits of resilient taxa like Sneathia, Fannyhessea and Dialister may confer resilience and enable recolonization, undermining long term treatment efficacy.

microbiology↗

bioRxiv2023

EnsembleSeq: A workflow towards real-time, rapid and simultaneous multi-kingdom amplicon sequencing for holistic and cost-effective microbiome research at scale

BackgroundBacterial communities are often concomitantly present with numerous microorganisms in the human body and other natural environments. Amplicon based microbiome studies have generally paid a skewed attention, that too at a rather shallow genus level resolution, to the highly abundant bacteriome, with interest now forking towards the other microorganisms, particularly fungi. Given the generally sparse abundance of other microbes in the total microbiome, simultaneous sequencing of amplicons targeting multiple microbial kingdoms could be possible even with full multiplexing. Guiding studies are currently needed for performing and monitoring multi-kingdom-amplicon sequencing and data capture at scale. MethodFull length bacterial 16S rRNA gene and entire fungal ITS region amplification was performed for human saliva samples (n=96, including negative and positive controls). Combined amplicon DNA libraries were prepared for nanopore sequencing using a major fraction of 16S molecules and a minor fraction of ITS amplicons. Sequencing was performed in a single run of an R10.4.1 flowcell employing the latest V14 chemistry. An approach for real time monitoring of the species saturation using dynamic rarefaction was designed as a guiding determinant of optimal run time. ResultsReal-time saturation monitoring for both bacterial and fungal species enabled the completion of sequencing within 30 hours, utilizing less than 60% of the total nanopores. [~]5 million HQ taxonomically assigned reads were generated ([~]4.2 million bacterial and 0.7 million fungal), providing a wider (beyond bacteriome) snapshot of human oral microbiota at species level resolution. Among the more than 400 bacterial and 240 fungal species identified in the studied samples, the species of Streptococcus (e.g. S. mitis, S. oralis) and Candida (e.g. C. albicans, C. tropicalis) were observed to be the dominating microbes in the oral cavity, respectively. This conformed well with the previous reports of the human oral microbiota. ConclusionEnsembleseq provides a proof-of-concept towards identification of both fungal and bacterial species simultaneously in a single fully multiplexed nanopore sequencing run in a time and resource effective manner. Details of this workflow are provided to enable large scale application for a holistic species level microbiome study.

microbiology↗

bioRxiv2020

Structural analysis of Sub16 sedolisin of Trichophyton rubrum reveals a flexible nature of its pro domain

Trichophyton rubrum is one of the leading causes of superficial skin infections worldwide. It is a keratinolytic fungus specialized in colonization of keratinized tissue of skin, hair and nails for long periods of time. The fungus encodes a wide repertoire of secreted proteases in its genome that not only aid in nutrient acquisition but also establishment of infection on the host. The proteases are synthesized in prepro form that requires removal of the prosegment for activation. In order to gain insights into the structural association of the pro domain with the catalytic domain, we investigate the structural features of the pro domain of the secreted sedolisin member Sub16 of T. rubrum. Our results show that the pro domain of Sub16 may have inherent flexibility in the absence of the associated catalytic domain which is stabilized in complex with catalytic domain. This is the first report of structural investigation on a stand-alone pro domain of sedolisin family of subtilases that will help in design of further structural studies of this protein.

biophysics↗

bioRxiv2020

Deletion of RsmE 16S rRNA methyltransferase leads to low level increase in aminoglycoside resistance in Mycobacterium smegmatis

Owing to its central role in cellular function, ribosome is one of the most common targets of antibiotics in bacteria. Mutations in rrs gene, ribosomal protein genes, methyltransfersases or drug influx/efflux are often found to overcome the drug response. Despite modulation of methylation pattern in the ribosome through mutations in the methyltransferases as one of key modulators of drug response, rsmG (gidB) is the only conserved methyltransferase associated with low-level drug resistance in large number of mycobacterial isolates. Here, we present the first evidence of association of methylation by mycobacterial RsmE, that methylates U1498 of 16S rRNA, with low levels of drug resistance. Deletion of the RsmE-homolog of Mycobacterium smegmatis leads to at least two-fold increase in the inhibitory concentration of aminoglycosides that bind in the decoding center proximal to U1498 in the 30S subunit. The change in inhibitory concentrations was highly specific and does not show any cross-resistance to drugs of other classes. Surprisingly, Rv2372c, the RsmE-homolog of Mycobacterium tuberculosis has the largest number of mutations among conserved ribosomal methyltransfersases, after gidB, highlighting the role of mutations in the RsmE methyltransferase as a key emerging mechanism of drug resistance in clinical strains of M. tuberculosis. Our work underlies the association of methylation by the RsmE-homolog with drug resistance and lays the groundwork to tackle this emerging mechanism of drug resistane in mycobacteria.

microbiology↗

bioRxiv2018

A novel mutation alters the stability of PapA2 resulting in the complete abrogation of sulfolipids in clinical mycobacterial strains

The analysis of whole genome has revealed specific geographical distribution of Mycobacterium tuberculosis (Mtb) strains across the globe suggestive of unique host dependent adaptive mechanisms in Mtb evolved out of selective pressures. We provide an important correlation of a genome-based mutation to a molecular phenotype across two predominant clinical Mtb lineages of the Indian subcontinent. We have identified a distinct lineage specific mutation-G247C, translating into an alanine to proline conversion in the papA2 gene of Indo oceanic lineage 1 [L1] Mtb strains; restoration of cell wall sulfolipids by simple genetic complementation of papA2 from lineage 3 [L3] or from H37Rv (Lineage 4-L4) attributed the loss of this glycolipid to this specific mutation in Indo oceanic L1 Mtb. Investigation into the structure of Mtb PapA2 revealed a distinct non-ribosomal peptide synthetase (NRPS) C domain conformation with an unconventional presence of Zinc binding motif. Surprisingly, the A83P mutation did not map to either the catalytic centre in the N-terminal subdomain or any of the substrate binding region of the protein. On the contrary, the inherent ability of mutant PapA2 to form insoluble aggregates and molecular simulations with the Wt/ mut PapA2 purports an important role for the surface associated 83rd residue in protein conformation. The present study demonstrates the importance of a critical structural residue in the papA2 protein of Mtb and helps establish a link between observed genomic alteration and its molecular consequence in the successful human pathogen Mtb.

molecular biology↗