Browsing by Author "Anand Prakash Maurya"

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Co-carriage of blaKPC-2 and blaNDM-1 in clinical isolates of Pseudomonas aeruginosa associated with hospital infections from India
(Public Library of Science, 2015) Deepjyoti Paul; Debadatta Dhar Chanda; Anand Prakash Maurya; Shweta Mishra; Atanu Chakravarty; Gauri Dutt Sharma; Amitabha Bhattacharjee
Global spread of KPC poses to be a serious threat complicating treatment options in hospital settings. The present study investigates the genetic environment of blaKPC-2 among clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital of India. The study isolates were collected from different wards and clinics of Silchar Medical College and Hospital, India, from 2012-2013. The presence of blaKPC was confirmed by genotypic characterization followed by sequencing. Cloning of the blaKPC-2 gene was performed and the genetic environment of this gene was characterized as well. Transferability of the resistance gene was determined by transformation assay and Southern hybridization. Additionally restriction mapping was also carried out. Two isolates of P. aeruginosa were found to harbor blaKPC-2 were resistant towards aminoglycosides, quinolone and β-lactam-β-lactamase inhibitor combination. In both the isolates, the resistance determinant was associated with class 1 integron and horizontally transferable. Both the isolates were co-harboring blaNDM-1. The first detection of this integron mediated blaKPC-2 coexisting with blaNDM-1 in P. aeruginosa from India is worrisome, and further investigation is required to track the gene cassette mediated blaKPC-2 in terms of infection control and to prevent the spread of this gene in hospitals as well as in the community. © 2015 Paul et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Design and synthesis of new benzimidazole-hybrids as anti-microbial agents: exploring the mechanistic insights as DNA gyrase inhibitors via in silico and in vitro based studies
(Taylor and Francis Ltd., 2025) Anand Prakash Maurya; Upendra Kumar Patel; Punit Tiwari; Gaurav Joshi; Roshan Kumar; Ragini Tilak; Alka K. Agarwal
Two series of antibacterial agents, 1,2,3-triazole and aminopyrimidine benzimidazole hybrids, were designed, synthesized, and characterized by IR, NMR, Mass spectroscopy, and X-ray crystallography studies. The biological studies revealed that compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 8d, 8e, 9d, 9e, 9f, 9h, 9j, and 9k exhibited significant antibacterial activity in vitro compared to the standard drug ciprofloxacin, against Gram-positive and Gram-negative bacterial strains. The study of hemotoxicity displayed a negligible toxicity profile for all the compounds. Furthermore, the mechanistic insights predicted via molecular docking studies on DNA gyrase revealed (Glide Scores) that compounds 5c and 5f possess better affinity within the active domain of DNA gyrase, which was further corroborated using molecular dynamics followed by direct DNA gyrase-based inhibition assays. Compound 5f was the most potent, while 5c showed an equipotent inhibition compared to a standard drug. © 2025 Informa UK Limited, trading as Taylor & Francis Group.
Design, synthesis, and antimicrobial evaluation of new triazole-tethered tetrazole hybrids via DNA gyrase inhibition
(Nature Research, 2025) Alka K. Agarwal; Vishal K. Singh; Anand Prakash Maurya; Sanjeev A. Kumar; Gaurav Joshi
To address the increasing Antimicrobial Resistance (AMR), we developed a library of triazole-tethered tetrazole derivatives using a multicomponent synthetic click chemistry strategy. It is well known that combining two or more types of pharmacophores into one molecule could afford a new entity with varied bioactivities. Considering this, the final products (6a–6o) were synthesized in excellent yields and were duly characterized using spectrometric analysis, including NMR and HRMS. To rationalize their biological attributes, synthetics were tested using different pathogenic microbial strains (S. aureus (ATCC 25923), S. epidermidis (ATCC 35984), E. coli (ATCC 25922), A. hydrophila (ATCC 7966), P. aeruginosa (ATCC 27853), S. typhi (Clinical isolate), S. typhimurium (Clinical isolate)). The antimicrobial potential (MIC µg/mL) of compounds compared to positive control ciprofloxacin revealed that compounds 6a, 6b, 6c, 6d, 6e, 6g, 6h, 6j, 6l, and 6m exhibited significant antibacterial activity with MIC 1.56-3.12 µg/mL in vitro compared to the ciprofloxacin against Gram-positive and Gram-negative bacterial strains. The molecules were further corroborated rationally using molecular modelling and dynamics analysis to assess their binding affinity with DNA gyrase. The study established that 6g and 6e possess a high affinity within the gyrase, as revealed by molecular docking analysis compared to ciprofloxacin. The molecular dynamics analysis for 6g revealed a stable conformation within the protein domain during the simulation period. The present work thus opens up the possibility of further exploring the utility of 6g and 6e in delineating their DNA gyrase binding biologically and deducing their mechanistic interventions. The work may further be expanded to recruit more pathogenic-resistant strains, and the inhibitory potential of the compounds may further be analysed. © The Author(s) 2025.
Diverse Genetic Array of blaCTXM-15 in Escherichia coli: A Single-Center Study from India
(Mary Ann Liebert Inc., 2016) Anand Prakash Maurya; Shweta Mishra; Anupam Das Talukdar; Debadatta Dhar Chanda; Atanu Chakravarty; Amitabha Bhattacharjee
CTX-M-15 is a chief contributor for expanded-spectrum cephalosporin and monobactam resistance in India, complicating treatment options. In this study, we have investigated genetic context of CTX-M-15 in Escherichia coli and their transmission dynamics in a tertiary referral hospital of India. A total of 198 isolates were collected, of which 66 were harboring blaCTXM-15. Among them, 14 isolates were carrying a single CTX-M-15 gene and 52 were harboring multiple extended-spectrum β-lactamase genes along with blaCTX-M-15. The resistance gene was flanked by tnpA, ISEcp1, IS26, and ORF477 in 10 different arrangements. The resistance determinant was horizontally transferable through F, W, I1, and P Inc types of plasmids. Restriction mapping of plasmids showed a variable band pattern even within the same Inc types. Minimum inhibitory concentration was found above the breakpoint level against expanded-spectrum cephalosporins and monobactam while susceptible against carbapenems. blaCTX-M-15 was highly stable and sustained in the cell after 115 serial passages. In pulse-field gel electrophoresis, eight pulsotypes of E. Coli were found to be responsible for the spread of blaCTX-M-15 in the tertiary referral center. We conclude that the presence of CTX-M-15 in the heterogeneous group of E. Coli is highly alarming in terms of infection control and it may require regular monitoring, so as to formulate appropriate antibiotic policy to stop the spread of this resistance determinant. © Copyright 2016, Mary Ann Liebert, Inc. 2016.
Expansion of highly stable bla OXA-10 β-lactamase family within diverse host range among nosocomial isolates of Gram-negative bacilli within a tertiary referral hospital of Northeast India
(BioMed Central Ltd., 2017) Anand Prakash Maurya; Debadatta Dhar; Mridul Kumar Basumatary; Deepjyoti Paul; Birson Ingti; Debarati Choudhury; Anupam Das Talukdar; Atanu Chakravarty; Shweta Mishra; Amitabha Bhattacharjee
Background: The current study reports dissemination of highly stable bla OXA-10 family of beta lactamases among diverse group of nosocomial isolates of Gram-negative bacilli within a tertiary referral hospital of the northern part of India. Methods: In the current study, a total number of 590 Gram negative isolates were selected for a period of 1 year (i.e. 1st November 2011-31st October 2012). Members of Enterobacteriaceae and non fermenting Gram negative rods were obtained from Silchar Medical College and Hospital, Silchar, India. Screening and molecular characterization of β-lactamase genes was done. Integrase gene PCR was performed for detection and characterization of integrons and cassette PCR was performed for study of the variable regions of integron gene cassettes carrying bla OXA-10. Gene transferability, stability and replicon typing was also carried out. Isolates were typed by ERIC as well as REP PCR. Results: Twenty-four isolates of Gram-negative bacilli that were harboring bla OXA-10 family (OXA-14, and OXA16) with fact that resistance was to the extended cephalosporins. The resistance determinant was located within class I integron in five diverse genetic contexts and horizontally transferable in Enterobacteriaceae, was carried through IncY type plasmid. MIC values were above break point for all the tested cephalosporins. Furthermore, co-carriage of bla CMY-2 was also observed. Conclusion: Multiple genetic environment of bla OXA-10 in this geographical region must be investigated to prevent dissemination of these gene cassettes within bacterial population within hospital settings. © 2017 The Author(s).
Genetic acquisition of NDM gene offers sustainability among clinical isolates of Pseudomonas aeruginosa in clinical settings
(Public Library of Science, 2015) Shweta Mishra; Supriya Upadhyay; Malay Ranjan Sen; Anand Prakash Maurya; Debarati Choudhury; Amitabha Bhattacharjee
New Delhi metallo β-lactamases are one of the most significant emerging resistance determinants towards carbapenem drugs. Their persistence and adaptability often depends on their genetic environment and linkage. This study reports a unique and novel arrangement of blaNDM-1 gene within clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital in north India. Three NDM positive clonally unrelated clinical isolates of P. aeruginosa were recovered from hospital patients. Association of integron with blaNDM-1 and presence of gene cassettes were assessed by PCR. Genetic linkage of NDM gene with ISAba125 was determined and in negative cases linkage in upstream region was mapped by inverse PCR. In which only one isolate's NDM gene was linked with ISAba125 for mobility, while other two reveals new genetic arrangement and found to be inserted within DNA directed RNA polymerase gene of the host genome detected by inverse PCR followed by sequencing analysis. In continuation significance of this novel linkage was further analyzed wherein promoter site detected by Softberry BPROM software and activity were assessed by cloning succeeding semi-quantitative RT-PCR indicating the higher expression level of NDM gene. This study concluded out that the unique genetic makeup of NDM gene with DNA-dependent-RNA-polymerase favours adaptability to the host in hospital environment against huge antibiotic pressure. © 2015 Mishra et al.
Genetic environment of plasmid mediated CTX-M-15 extended spectrum beta-lactamases from clinical and food borne bacteria in north-eastern India
(Public Library of Science, 2015) Supriya Upadhyay; Abbas Hussain; Shweta Mishra; Anand Prakash Maurya; Amitabha Bhattacharjee; Santa Ram Joshi
Background The study investigated the presence of CTX-M-15 type extended spectrum beta-lactamases (ESBL), compared their genetic arrangements and plasmid types in gram negative isolates of hospital and food origin in north-east India. From September 2013 to April 2014, a total of 252 consecutive, non-duplicate clinical isolates and 88 gram negative food isolates were selected. Phenotypic and molecular characterization of ESBL genes was performed. Presence of integrons and gene cassettes were analyzed by integrase and 59 base-element PCR respectively. The molecular environments surrounding blaCTX-M and plasmid types were investigated by PCR and PCR-based replicon typing respectively. Transformation was carried out to assess plasmid transfer. Southern blotting was conducted to localize the blaCTX-M-15 genes. DNA fingerprinting was performed by ERIC-PCR. Results Prevalence of ESBL was found to be 40.8% (103/252) in clinical and 31.8% (28/88) in foodborne isolates. Molecular characterization revealed the presence of 56.3% (58/103) and 53.5% (15/28) blaCTX-M-15 in clinical and food isolates respectively. Strains of clinical and food origin were non-clonal. Replicon typing revealed that IncI1 and IncFII plasmid were carrying blaCTX-M-15 in clinical and food isolates and were horizontally transferable. The ISEcp1 element was associated with blaCTX-M-15 in both clinical and food isolates. Conclusions The simultaneous presence of resistance determinants in non-clonal isolates of two different groups thus suggests that the microbiota of common food products consumed may serve as a reservoir for some of the drug resistance genes prevalent in human pathogens. © 2015 Upadhyay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction to nanogels: exploring the frontier of nanoscale technology
(Elsevier, 2025) Snigdha Singh; Anand Prakash Maurya; Anurag Kumar Singh; Vivek K. Chaturvedi; Jay Singh; Amit Kumar Singh; Santosh Kumar Singh
Drug delivery holds great promise for the development of nanogel-based platforms. Owing to their exceptional stability and efficient drug-loading capacity for both hydrophilic and hydrophobic agents, nanogels present significant opportunities for pharmaceutical innovation. As multifunctional systems, composite nanogels can deliver genes, drugs, and diagnostic agents, making them ideal platforms for multimodal theranostic applications. These nanogels can respond to various stimuli, enabling the controlled release of chemotherapy and immunotherapy drugs while reprogramming cells within the tumor microenvironment to suppress tumor growth, progression, and metastasis. Specific ligands can be attached to nanogels for active targeting to enhance drug accumulation and improve therapeutic precision, ultimately improving cancer treatment outcomes. Additionally, advanced “immune-specific” nanogels possess tumor tissue-editing capabilities, further refining targeted drug delivery. Integrating multifunctional nanogel-based delivery systems enhances the precision and effectiveness of immunotherapy and combination therapies, offering improved outcomes in tumor treatment. © 2025 Elsevier Ltd. All rights reserved.
Occurrence of co-existing bla VIM-2 and bla NDM-1 in clinical isolates of Pseudomonas aeruginosa from India
(BioMed Central Ltd., 2016) Deepjyoti Paul; Debadatta Dhar; Anand Prakash Maurya; Shweta Mishra; Gauri Dutt Sharma; Atanu Chakravarty; Amitabha Bhattacharjee
Background: bla VIM-2 harboring Pseudomonas aeruginosa has been reported worldwide and considered as the most prevalent metallo-β-lactamase after NDM which are found horizontally transferable and mostly associated with integron gene cassettes. The present study investigates the genetic background, transmission dynamics as well as stability of bla VIM-2 in clinical isolates of P. aeruginosa harbor bla NDM-1 as well which were collected from October 2012 to September 2013. Methods: Two P. aeruginosa strains harboring bla VIM-2 along with bla NDM-1 were isolated from Silchar Medical College and Hospital, India. Genetic environment of these resistance determinants was determined and transferability was checked by transformation and conjugation assay which was further confirmed by Southern hybridization. Replicon typing was performed to determine the incompatibility group of the resistant plasmid and their stability was checked by serial passage method. Antimicrobial susceptibility pattern of the isolates was determined and their clonal relatedness was checked by pulsed field gel electrophoresis. Results: bla VIM-2 was found to be horizontally transferable through an Inc F type plasmid of approximately 30 kb in size. bla VIM-2 was found to be associated with integron gene cassette and was flanked by two different types of cassette arrays. Both the isolates were co-harboring bla NDM-1 which was carried within Inc N type of plasmid with an approximate 24 kb in size and associated with ISAba125 in their upstream region. Reduced susceptibility rate as well as high MIC range was observed in case of wild strains and transformants carrying bla VIM-2 and bla NDM-1. Conclusions: The detection of this co-existence of multiple carbapenem resistance genes in this part of world is worrisome and further investigation is required in order to trace the source and to initiate proper treatment option. © 2016 The Author(s).
Porous silicon nanocarriers for the management of neurodegenerative disorders
(Elsevier, 2025) Devinder Kumar; Raj N. Kumar; Sunil Dutt; Pankaj Kalia; Snigdha Singh; Anand Prakash Maurya; Anurag Kumar Singh; Rajendra Awasthı; Santosh Kumar Singh
Porous silicon (PSi) nanocarriers are gaining a lot of attention in nanomedicine for the treatment of neurodegenerative diseases (NDs). Aside from their complicated pathophysiology, NDs, such as Parkinson's and Alzheimer's, present unique challenges due to the difficulty for therapeutic agents to cross the blood–brain barrier. Since PSi nanocarriers have tunable porosity, biocompatibility, and biodegradability, they enable the effective loading and controlled release of a variety of therapeutic agents. Due to its porous structure and large surface area, peptides, nucleic acids, and small molecules are encapsulated in PSi, improving the bioavailability and therapeutic efficacy of the drugs. As recent findings show, it is now possible to make pSi nanoparticles to deliver neuroprotective agents directly to targeted neuronal cells, improving treatment outcomes. Delivery of therapeutics to specific brain regions can be enabled by functionalizing PSi with specific ligands or antibodies, improving its targeting capabilities. In addition, since conventional treatments often require high dosages and frequent administration, the ability of PSi nanocarriers to support sustained drug release can significantly reduce side effects. With PSi's controlled release profile, therapeutic drug levels can be maintained in the bloodstream for extended periods, improving patient compliance and overall treatment effectiveness. Pharmaceutical administration is not the only use for PSi nanocarriers; they have also shown promise in diagnostic applications, allowing simultaneous imaging and monitoring of treatment effects. Due to its dual purpose, PSi positions itself as a flexible platform for theranostic applications in of neurological diseases. Despite encouraging developments, there are still difficulties in the clinical implementation of PSi-based therapies. Research is presently being carried out on their synthesis and surface modification to improve the stability and mitigate the potential toxicity of pSi nanoparticles. To enable their integration into clinical practice, issues related to large-scale manufacturing and regulatory approval processes must also be resolved. © 2026 Elsevier Inc. All rights reserved.
Recent Developments in Nanotechnology-Based Therapeutics for the Treatment of Alzheimer’s Disease
(CRC Press, 2025) Harsh Yadav; P. Subash; Satish Dubey; Anand Prakash Maurya; Ramu Singh; Sabyasachi Maiti
Alzheimer's disease (AD) seems to be a neurodegenerative disease that strikes people of any age. Loss of recent memory, thinking, problem-solving, and reasoning skills is the first sign of a slow decline in brain function. Alzheimer's disease has a significant economic impact, affecting around 37 million individuals worldwide. The pathophysiology of Alzheimer's disease is influenced by plaques of aggregated-ß amyloid (Aß) and synaptotoxic Aß, as well as tau phosphorylation, which results in the formation of neurofibrillary tangles. Existing Alzheimer's drugs might help reduce symptoms and improve life for people with the disease. However, they have failed horribly at stopping the disease from worsening and making it curable. Also, the blood-brain barrier, which surrounds the CNS, makes it hard to get drugs to the nervous system to treat AD, which lowers the therapeutic bioavailability. Many nanoparticle technologies can get around these problems and get the medicine to the CNS. The goal of this chapter is to summarize and spotlight recent advances in nanotechnology-based therapies and what they mean for treating Alzheimer’s. © 2025 selection and editorial matter, Vaishali Manikrao Patil, Dileep Kumar, Neeraj Masand; individual chapters, the contributors.