Somesh Baranwal

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), results in substantial economic losses in global poultry production. The emergence of multidrug-resistant (MDR) APEC poses zoonotic risks through horizontal transfer of antimicrobial resistance (AMR) genes. Bacteriophage therapy emerges as a safe alternative to antibiotherapy; however, comprehensive characterization of phages targeting MDR-APEC from diverse geographical regions remains limited. We isolated five lytic bacteriophages from poultry fecal samples collected from five Indian states and characterized them through morphological analysis, physiological stability testing, whole-genome sequencing, and in vivo efficacy assessment. Host range was determined against APEC isolates, and therapeutic potential was validated in the Galleria mellonella infection model. All phages showed Myovirus-like morphology and stability across physiologically relevant temperatures (up to 55°C–70°C) and pH conditions (3–11). Phages were classified as Escherichia phage vB_EcoM_fRPOT1, vB_EcoM_fDMYT1, vB_EcoM_fBSZT1, vB_EcoM_fUAMT1, and vB_EcoM_fPKPT2. Their genome size ranges from 170 to 356 kb, belonging to three distinct genera: Dhakavirus , Gaprivervirus , and Asteriusvirus . Genomic analysis confirmed the absence of antimicrobial resistance, virulence, toxin, or lysogeny genes. Fifty-one APEC strains were isolated, of which 23 (45.1%) were MDR. Individual phages lysed 37%–51% of tested APEC and 17%–39% of MDR strains. Three phages (fBSZT1, fUAMT1, and fPKPT2) significantly improved larval survival to 60%–80% at an MOI of 10 in G. mellonella infection models compared to the untreated control. This study establishes a well-characterized phage bank targeting MDR-APEC strains, providing a foundation for developing phage-based interventions to reduce antibiotic dependency and mitigate AMR transmission risks under the One Health framework. IMPORTANCE: The overuse of antibiotics in poultry farming has created a crisis. The multidrug-resistant (MDR) bacteria threaten both animal health and human safety through the food chain. When antibiotics fail, farmers face devastating losses, and resistant bacteria can transfer to humans through consumption or environmental contamination. Bacteriophages offer a practical solution as they kill target bacteria without harming beneficial microbes or leaving chemical residues. Our comprehensive characterization confirms that these five phages are safe and effective as they lack any resistance or toxin genes and rescue 60%–80% of infected larvae. This represents a characterized phage bank targeting the specific resistant strains in Indian poultry. By providing a validated alternative to antibiotics, this work supports sustainable food production while reducing the spread of antimicrobial resistance from farms to humans.

Colibacillosis, caused by Avian Pathogenic Escherichia coli (APEC), result in substantial economic losses in global poultry production. The emergence of multidrug-resistant (MDR) APEC poses zoonotic risks through horizontal transfer of antimicrobial resistance (AMR) genes. Bacteriophage therapy emerges as a safe alternative to antibiotherapy; however, comprehensive characterization of phages targeting MDR-APEC from diverse geographical regions remains limited. We isolated five lytic bacteriophages from poultry fecal samples collected from five Indian states and characterized them through morphological analysis, physiological stability testing, whole-genome sequencing, and in vivo efficacy assessment. Host range was determined against APEC isolates, and therapeutic potential was validated in Galleria mellonella infection model. All five phages showed Myovirus-like morphology and stability across physiologically relevant temperatures (up to 55-70°C) and pH conditions (3-11). Their genome size ranges from 170 to 356 kb, belonging to three distinct genera; Dhakavirus, Gaprivervirus, and Asteriusvirus. Genomic analysis confirmed absence of antimicrobial resistance, virulence, toxin, or lysogeny genes. 51 APEC strains were isolated, of which 23 (45.1%) were MDR. Individual phages lysed 37-51% of tested APEC and 17-39% of MDR strains. Three Escherichia phages (fBSZT1, fUAMT1, fPKPT2) significantly improved larval survival to 60-80% at MOI 10 in G. mellonella infection models compared to untreated controls. This study establishes a well-characterized phage bank targeting MDR-APEC strains, providing foundation for developing phage-based interventions to reduce antibiotic dependency and mitigate AMR transmission risks under One Health framework.

Base-mediated chemoselective synthesis of C3-styryl-functionalized mono-ester and di-ester substituted novel pyrrole derivatives under ambient conditions has been achieved.

Breast cancer (BC) remains the foremost cause of cancer mortality in women, with ER + subtypes accounting for over 70% of cases. Disease progression is driven by aberrant receptor signaling, marked by elevated ERα and diminished ERβ expression, underscoring the urgency of potent and targeted ERα inhibitors. Although selective estrogen receptor modulators like tamoxifen have significantly improved patient survival, their clinical utility is constrained by adverse effects like endometrial carcinoma, blood clot formation, deep vein thrombosis, hot flashes and VTE, alongside emergence of drug resistance. To overcome current limitations in ERα targeted therapy, we designed and synthesized a novel series of indole-conjugated isoxazole/ isoxazoline hybrids through a streamlined five-step synthetic route, affording moderate to high yields (70–90%). These hybrids were systematically evaluated against ERα-predominant and triple-negative BC cell lines, with promising candidates subjected to healthy cell cytotoxicity, receptor inhibition assays and comprehensive in silico validation. Among the synthesized hybrids, C04 and C06 emerged as lead candidates, demonstrating markedly superior anti-proliferative activity on ERα dominant BC cells compare to tamoxifen and bazedoxifene. Cell cycle arrest and apoptotic studies further confirmed capability of both compounds in apoptosis induction primarily through G0/G1 cell-cycle arrest. ERα inhibition assays highlighted the exceptional potency of C06, exceeding bazedoxifene by 3.3-fold and tamoxifen by 7.9-fold. C04 was identified with broad safety profile in HEK cell cytotoxicity studies. Molecular docking and dynamic simulations further validated their robust target engagement. Collectively, these findings established C04 and C06 as optimistic ERα targeted leads with superior efficacy and safety profiles than standard drug candidates.

Here, we describe a Bacillus subtilis bacteriophage isolated from sewage water. The phage fHSPT3 was isolated against the host Bacillus subtilis 168 and has a genome size of 150,187 bp with 221 protein-coding sequences. The fHSPT3 belongs to the genus Siophivirus , lacks virulence or antibiotic resistance genes, and shows a virulent life cycle predicted through PhageScope and PhageAI.