| Title | Potential Use of Mycobacterium paragordonae for Antimycobacterial Drug Screening Systems |
|---|---|
| Author | Ga‑Yeong Cha1,2,6, Hyejun Seo1,4, Jaehun Oh1,2,6, Byoung‑Jun Kim1, and Bum‑Joon Kim1,2,3,4,5,6* |
| Address | 1Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea, 2Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea, 3Liver Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea, 4Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea, 5Institute of Endemic Diseases, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of Korea, 6BK21 Four Biomedical Science Project, College of Medicine, Seoul National University, Seoul, Republic of Korea |
| Bibliography | Journal of Microbiology, 61(1),121-129, 2023, |
| DOI | 10.1007/s12275-022-00009-1 |
| Key Words | Mycobacterium paragordonae (Mpg) · Recombinant mycobacteria · Amoebae · Acanthamoeba castellanii · Antimycobacterial drug screening system |
| Abstract | Our recent genome-based study indicated that Mycobacterium paragordonae (Mpg) has evolved to become more adapted to an intracellular lifestyle within free-living environmental amoeba and its enhanced intracellular survival within Acanthamoeba castellanii was also proved. Here, we sought to investigate potential use of Mpg for antimycobacterial drug screening systems. Our data showed that Mpg is more susceptible to various antibiotics compared to the close species M. marinum (Mmar) and M. gordonae, further supporting its intracellular lifestyle in environments, which would explain its protection from environmental insults. In addition, we developed two bacterial whole-cell-based drug screening systems using a recombinant Mpg stain harboring a luciferase reporter vector (rMpg-LuxG13): one for direct application to rMpg-LuxG13 and the other for drug screening via the interaction of rMpg-LuxG13 with A. castellanii. Direct application to rMpg-LuxG13 showed lower inhibitory concentration 50 ( IC50) values of rifampin, isoniazid, clarithromycin, and ciprofloxacin against Mpg compared to Mmar. Application of drug screening system via the interaction of rMpg-LuxG13 with A. castellanii also exhibited lower IC50 values for rifampin against Mpg compared to Mmar. In conclusion, our data indicate that Mpg is more susceptible to various antibiotics than other strains. In addition, our data also demonstrate the feasibility of two whole cellbased drug screening systems using rMpg-LuxG13 strain for the discovery of novel anti-mycobacterial drugs. |