Polycationic phosphorous dendrimer potentiates multiple antibiotics against drug-resistant mycobacterial pathogens.

Autor: Imran M; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Singh S; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India., Ahmad MN; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Malik P; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Mukhopadhyay A; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Yadav KS; Division of Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Gupta UD; National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra 282001, India., Mugale MN; Division of Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Mitra K; Electron Microscopy Unit, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Srivastava KK; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Chopra S; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Mignani S; Centre d'Etudes et de Recherche sur le Medicament de Normandie (CERMN), Université de Caen Normandie, Caen 14032, France; Centro de Quimica da Madeira, MMRG, Campus da Penteada, Universidade da Madeira, Funchal 9020-105 19, Portugal. Electronic address: serge.mignani@staff.uma.pt., Apartsin E; Université de Bordeaux, CNRS, Bordeaux INP, CBMN, UMR 5248, Pessac F-33600, France., Majoral JP; Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099, 31077 Toulouse Cedex 4, France; LCC-CNRS, Université de Toulouse, CNRS, Toulouse 31400, France. Electronic address: jean-pierre.majoral@lcc-toulouse.fr., Dasgupta A; Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: a.dasgupta@cdri.res.in.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Apr; Vol. 173, pp. 116289. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1016/j.biopha.2024.116289
Abstrakt: Mycobacterium tuberculosis (Mtb), causative agent of tuberculosis (TB) and non-tubercular mycobacterial (NTM) pathogens such as Mycobacterium abscessus are one of the most critical concerns worldwide due to increased drug-resistance resulting in increased morbidity and mortality. Therefore, focusing on developing novel therapeutics to minimize the treatment period and reducing the burden of drug-resistant Mtb and NTM infections are an urgent and pressing need. In our previous study, we identified anti-mycobacterial activity of orally bioavailable, non-cytotoxic, polycationic phosphorus dendrimer 2G0 against Mtb. In this study, we report ability of 2G0 to potentiate activity of multiple classes of antibiotics against drug-resistant mycobacterial strains. The observed synergy was confirmed using time-kill kinetics and revealed significantly potent activity of the combinations as compared to individual drugs alone. More importantly, no re-growth was observed in any tested combination. The identified combinations were further confirmed in intra-cellular killing assay as well as murine model of NTM infection, where 2G0 potentiated the activity of all tested antibiotics significantly better than individual drugs. Taken together, this nanoparticle with intrinsic antimycobacterial properties has the potential to represents an alternate drug candidate and/or a novel delivery agent for antibiotics of choice for enhancing the treatment of drug-resistant mycobacterial pathogens.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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