Luciferase reporter mycobacteriophage (TM4:: GeNL ) enables rapid assessment of drug susceptibilities and inducible macrolide resistance in Mycobacterium abscessus complex

Mycobacterium abscessus (MAB) is a notorious human pathogen causing severe infections in individuals with cystic fibrosis and immunocompromised patients. Treatment options for MAB are very limited as they are resistant to multiple drugs through intrinsic and acquired resistance mechanisms. While mac...

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Bibliographic Details
Published in:Journal of clinical microbiology Vol. 63; no. 9; p. e0084125
Main Authors: Rajagopalan, Saranathan, Das, Lahari, Kohlerschmidt, Donna J., Rourke, Amy K., Shakir, Salika M., Larsen, Michelle H., O’Donnell, Max R., Szymczak, Wendy A., Escuyer, Vincent E., Thwe, Phyu M., Jacobs, William R.
Format: Journal Article
Language:English
Published: United States American Society for Microbiology 10.09.2025
Subjects:
amikacin
Amikacin - pharmacology
Anti-Bacterial Agents - pharmacology
Clarithromycin - pharmacology
Drug Resistance, Bacterial - genetics
erm
Genes, Reporter
Humans
inducible macrolide resistance
luciferase reporter mycobacteriophage
Luciferases - genetics
Macrolides - pharmacology
Microbial Sensitivity Tests - methods
Mycobacteriology
Mycobacteriology and Aerobic Actinomycetes
Mycobacteriophages - drug effects
Mycobacteriophages - genetics
Mycobacterium abscessus
Mycobacterium abscessus - drug effects
Mycobacterium abscessus - genetics
Mycobacterium abscessus - virology
Mycobacterium Infections, Nontuberculous - microbiology
Special Series: Diagnostic Testing for Mycobacteria
erm
amikacin
inducible macrolide resistance
luciferase reporter mycobacteriophage
Mycobacterium abscessus
ISSN:0095-1137, 1098-660X, 1098-660X
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Summary:Mycobacterium abscessus (MAB) is a notorious human pathogen causing severe infections in individuals with cystic fibrosis and immunocompromised patients. Treatment options for MAB are very limited as they are resistant to multiple drugs through intrinsic and acquired resistance mechanisms. While macrolides and amikacin are the key drugs in the fight against MAB infections, emerging drug resistance is compromising their efficacy. Current growth-based drug susceptibility testing (DST) method takes 7 to 14 days to identify clarithromycin susceptibility due to the presence of inducible macrolide resistance and 3 to 5 days for other drugs. We developed a novel luciferase reporter mycobacteriophage (LRM) based phenotypic DST method using TM4:: GeNL to assess MAB drug susceptibility based on metabolic inhibition rather than growth. LRM-DST significantly reduces the DST turnaround time to 48 h and provides rapid assessment of MAB susceptibility to drugs, including inducible macrolide resistance, thereby accelerating the treatment process and improving patient outcomes.
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ISSN:0095-1137
1098-660X
1098-660X
DOI:10.1128/jcm.00841-25