Browsing by Author "Vidyasagar"

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A novel nanotherapeutic approach: Dual action of green-synthesized silver nanoparticles from Clerodendrum serratum against MDR-ESKAPE pathogens with wound healing potential
(Editions de Sante, 2025) Ritu Raj Patel; Pandey Priya Arun; Vidyasagar; Aradhana Mishra; Sudhir Kumar Singh; Samer Singh; Brahmeshwar Mishra; Meenakshi Singh
The rapid emergence of multidrug-resistant (MDR) ESKAPE pathogens in healthcare settings, particularly chronic wound infections presents a critical challenge. Moreover, with antibiotic resistance reaching alarming levels and conventional treatments failing against biofilm-associated infections, there is an urgent need to develop novel and effective therapeutic strategies. In this study, silver nanoparticles (AgNPs) synthesized via a green method using Clerodendrum serratum leaf extract, along with their polyethylene glycol-coated derivative (PEG-AgNPs), were evaluated for their antibacterial and wound-healing potential. PEG-AgNPs demonstrated superior antibacterial efficacy, with significantly lower minimum inhibitory concentration (MIC) values (0.3906–12.5 μg/mL) compared to AgNPs (3.125–25 μg/mL). Time-kill studies further confirmed that PEG-AgNPs exhibited enhanced bactericidal properties. Mechanistic investigations revealed that their antibacterial activity resulted from bacterial cell membrane rupture, leading to cytoplasmic content leakage, as confirmed by FACS analysis. Furthermore, biofilm formation by these pathogens was evaluated, and the nanoparticles demonstrated remarkable anti-biofilm potency, particularly against Acinetobacter baumannii and Pseudomonas aeruginosa. The LC-MS analysis of C. serratum leaf extract revealed bioactive phytoconstituents, which were subjected to molecular docking studies against biofilm-forming factors in P. aeruginosa and A. baumannii confirming strong binding interactions. Additionally, the prepared nanoparticle-based gel formulations significantly enhanced in vivo wound healing in both uninfected and infected (A. baumannii and P. aeruginosa) wounds, highlighting their potential as dual-action therapeutic agents for inhibiting MDR pathogens and simultaneously promoting tissue regeneration. Therefore, these findings suggest that green synthesized nanoparticles, particularly PEG-AgNPs hold promise as novel interventions for combating MDR-ESKAPE infected wounds. © 2025 Elsevier B.V.
Facile green synthesis of silver nanoparticles derived from the medicinal plant Clerodendrum serratum and its biological activity against Mycobacterium species
(Elsevier Ltd, 2024) Vidyasagar; Ritu Raj Patel; Sudhir Kumar Singh; Deepa Dehari; Gopal Nath; Meenakshi Singh
The emergence of multidrug-resistant mycobacterial strains is a significant crisis that has led to higher treatment failure rates and more toxic and expensive medications for tuberculosis (TB). The urgent need to develop novel therapeutics has galvanized research interest towards developing alternative antimicrobials such as silver nanoparticles (AgNPs). The current study focused on the anti-mycobacterial activity of green-synthesized AgNPs and its polyethylene glycol encapsulated derivative (PEG-AgNPs) with improved stability using the leaves extract of Clerodendrum serratum. Different characterization methods were used to analyze them. DLS analysis revealed a lower polydispersity index of PEG-AgNPs, suggesting a more uniform size distribution than that of AgNPs. The HR-TEM results revealed that the AgNPs and PEG-AgNPs have predominantly spherical shapes in the size range of 9–35 nm and 15–60 nm, respectively, while positive values of Zeta potential indicate their stability. FTIR-ATR analysis confirmed the presence of functional groups responsible for reducing and capping the bio-reduced AgNPs, whereas the XRD data established its crystalline nature. Impressively, the PEG-AgNPs exhibited maximum inhibitory activity against different Tubercular and Non-Tuberculous Mycobacterium species i.e., Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium marinum, relative to those of AgNPs and Linezolid. The flow cytometry assay showed that the anti-mycobacterial action was mediated by an increase in cell wall permeability. Notably, the results of AFM confirm their ability to inhibit mycobacterial biofilm significantly. We demonstrated the nontoxic nature of these AgNPs, explicated by the absence of hemolytic activity against human RBCs. Overall, the results suggest that PEG-AgNPs could offer a novel therapeutic approach with potential anti-mycobacterial activity and can overcome the limitations of existing TB therapies. © 2024 The Authors
Recent advances in inhibitor development and metabolic targeting in tuberculosis therapy
(Academic Press, 2025) Ritu Raj Patel; Vidyasagar; Sudhir Kumar Singh; Meenakshi Singh
Despite being a preventable and treatable disease, tuberculosis (TB) remained the second leading infectious cause of death globally in 2022, surpassed only by COVID-19. The death rate from TB is influenced by numerous factors that include antibiotic drug resistance, noncompliance with chemotherapy by patients, concurrent infection with the human immunodeficiency virus, delayed diagnosis, varying effectiveness of the Bacille-Calmette-Guerin vaccine, and other factors. Even with the recent advances in our knowledge of Mycobacterium tuberculosis and the accessibility of advanced genomic tools such as proteomics and microarrays, alongside modern methodologies, the pursuit of next-generation inhibitors targeting distinct or multiple molecular pathways remains essential to combat the increasing antimicrobial resistance. Hence, there is an urgent need to identify and develop new drug targets against TB that have unique mechanisms. Novel therapeutic targets might encompass gene products associated with various aspects of mycobacterial biology, such as transcription, metabolism, cell wall formation, persistence, and pathogenesis. This review focuses on the present state of our knowledge and comprehension regarding various inhibitors targeting key metabolic pathways of M. tuberculosis. The discussion encompasses small molecule, synthetic, peptide, natural product and microbial inhibitors and navigates through promising candidates in different phases of clinical development. Additionally, we explore the crucial enzymes and targets involved in metabolic pathways, highlighting their inhibitors. The metabolic pathways explored include nucleotide synthesis, mycolic acid synthesis, peptidoglycan biosynthesis, and energy metabolism. Furthermore, advancements in genetic approaches like CRISPRi and conditional expression systems are discussed, focusing on their role in elucidating gene essentiality and vulnerability in Mycobacteria. © 2025 Elsevier Ltd