Biology subjects

Sahu, M.

Publications and source records attributed to Sahu, M..

3 recordsLinked to original sources

bioRxiv2026

Exploration of Bacteriophages Against Vancomycin-Resistant Enterococcus faecium: A Report from India

The vancomycin-resistant Enterococcus faecium (VREfm) has been declared as a high priority pathogen by World Health Organisation (WHO). It presents a major therapeutic challenge to healthcare, remaining with limited antibiotic options. Bacteriophage therapy has emerged as a promising alternative for combating antimicrobial-resistant pathogens. This study reports the isolation and characterization of bacteriophages active against VREfm and MDR E. faecium clinical isolates from India. Two bacteriophages, NIMS_EF375_N69_P9 ({Phi}1) and NIMS_EF375_N74_P12 ({Phi}2), were isolated from sewage by enrichment using MDR E. faecium strain EF375 as the propagation host. Lytic activity was confirmed by spot assay and double-layer soft agar plaque assay; both phages produced clear plaques of 1.5-2.0 mm. Transmission electron microscopy showed icosahedral heads with long non-contractile tails, presenting siphovirus-like morphotype within the class Caudoviricetes. Host range was assessed against 10 MDR E. faecium isolates (including the propagation host), 2 of which were VREfm. {Phi}1 lysed 5 of 10 isolates, including the VanA-type VREfm, whereas {Phi}2 lysed 7 of 10, including both VanA- and VanB-type VREfm. In time-kill assays against EF375 at an MOI of 1, {Phi}1 produced effective decline in optical density sustained through 24 h ([~]80% reduction relative to the untreated control), whereas {Phi}2 suppressed bacterial growth with only [~]50% reduction. To the best of our knowledge, this study represents the first report from India on the isolation and characterization of bacteriophages active against clinical VREfm isolates. The broader host range of {Phi}2 and the stronger killing kinetics of {Phi}1 suggest complementary roles in a phage cocktail, warranting genomic characterization and in vivo evaluation.

microbiology↗

bioRxiv2023

YAP1 status defines two intrinsic subtypes of LCNEC with distinct molecular features and therapeutic vulnerabilities

Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like the more common small cell lung cancer (SCLC), is associated with an absence of druggable oncogenic driver mutations, a clinically aggressive disease course, and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies which are, instead, often adapted from SCLC and non-small cell lung cancer (NSCLC) approaches. While there have been some efforts to describe the molecular landscape of LCNEC, to date there are few links between distinct biologic phenotypes of LCNEC and therapeutic vulnerabilities. Here, we demonstrate that the presence or absence of the transcription factor YAP1 distinguishes two roughly equal subsets of LCNEC. The YAP1-high subset is mesenchymal and inflamed and characterized, alongside TP53 mutations, by co-occurring alterations in CDKN2A/B and SMARCA4. Therapeutically, the YAP1-high subset demonstrates vulnerability to MEK and AXL targeting strategies, including a novel preclinical AXL CAR-T cell, as well as predicted vulnerability to SMARCA2 degraders and CDK4/6 inhibitors. Meanwhile, the YAP1-low subset is epithelial and immune-cold and more commonly features TP53 and RB1 co-mutations, similar to those observed in pure SCLC. Notably, the YAP1-low subset is also characterized by expression of SCLC subtype-defining transcription factors -especially ASCL1 and NEUROD1 - and, as expected given its transcriptional similarities to SCLC, exhibits putative vulnerabilities reminiscent of SCLC, including Delta-like ligand 3 (DLL3) and CD56 targeting, as with novel preclinical DLL3 and CD56 CAR T-cells, and DNA damage repair (DDR) inhibition. These findings highlight the potential for YAP1 to guide the first personalized treatment strategies for LCNEC.

cancer biology↗

bioRxiv2022

Symbolic quantitative cognition in wild zebrafish (Danio rerio)

Zebrafish (Danio rerio) constitute an excellent model system to investigate the neural and genetic basis of quantitative cognition We tested the ability of reward quantity discrimination of wild-type zebrafish in an associative learning task. We used an operant conditioning paradigm in which the number of horizontal lines zebrafish approached in a 2-alternative forced choice task predicted the number of food reward pellets they would receive. Zebrafish did not learn a preference for the 2-line stimulus predictive of receiving 2 food pellets. However, a subset of the fish performed significantly above chance in a discrimination task with the same apparatus, in which the 2-line stimulus was associated with the same reward but the choice of the 1-line stimulus was not rewarded. Zebrafish also showed a population level learning in a simpler spatial association task with the same apparatus. We also explored the explanatory value of alternative spatial learning hypotheses such as a Win-Stay, Lose-Shift (WSLS) strategy at the individual level for fish in navigating these spatially randomised tasks.

animal behavior and cognition↗