» Articles » PMID: 39189762

Characterization of Novel Double-reporter Strains of for Drug Discovery: a Study in MScarlet

Overview
Specialty Microbiology
Date 2024 Aug 27
PMID 39189762
Authors
Affiliations
Soon will be listed here.
Abstract

Importance: (Mab) is currently considered an "incurable nightmare." Its intrinsic resistance, high toxicity, long duration, and low cure rates of available therapies often lead to the clinical decision not to treat. Moreover, one of the significant drawbacks of anti-Mab drug development is the lack of correlation between susceptibility and clinical efficacy. Most drug screening assays are performed on Mab growing in liquid cultures. But being an intracellular pathogen, inducing granulomas and biofilm formation, the broth culture is far from ideal as drug-testing setup. This study presents new double-reporter Mab strains that allow direct real-time bacterial detection and quantification in a non-invasive way. These strains can be applied to an extensive range of experimental settings, far surpassing the utility of single-reporter bacteria. They can be used in all steps of the pre-clinical anti-Mab drug development pipeline, constituting a highly valuable tool to increase its success.

References
1.
Kwak N, Dalcolmo M, Daley C, Eather G, Gayoso R, Hasegawa N . pulmonary disease: individual patient data meta-analysis. Eur Respir J. 2019; 54(1). DOI: 10.1183/13993003.01991-2018. View

2.
Larsson M, Lerm M, Angeby K, Nordvall M, Jureen P, Schon T . A luciferase-based assay for rapid assessment of drug activity against Mycobacterium tuberculosis including monitoring of macrophage viability. J Microbiol Methods. 2014; 106:146-150. DOI: 10.1016/j.mimet.2014.08.015. View

3.
Brown-Elliott B, Rubio A, Wallace Jr R . Susceptibility Testing of a Novel Benzimidazole, SPR719, against Nontuberculous Mycobacteria. Antimicrob Agents Chemother. 2018; 62(11). PMC: 6201134. DOI: 10.1128/AAC.01503-18. View

4.
Wu M, Aziz D, Dartois V, Dick T . NTM drug discovery: status, gaps and the way forward. Drug Discov Today. 2018; 23(8):1502-1519. PMC: 6078814. DOI: 10.1016/j.drudis.2018.04.001. View

5.
Silva T, Moreira A, Nazmi K, Moniz T, Vale N, Rangel M . Lactoferricin Peptides Increase Macrophages' Capacity To Kill . mSphere. 2017; 2(4). PMC: 5577653. DOI: 10.1128/mSphere.00301-17. View