Potential Use of Mycobacterium paragordonae for Antimycobacterial Drug Screening Systems

Ga-Yeong Cha; Hyejun Seo; Jaehun Oh; Byoung-Jun Kim; Bum-Joon Kim

doi:10.1007/s12275-022-00009-1

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Potential Use of Mycobacterium paragordonae for Antimycobacterial Drug Screening Systems: Ga-Yeong Cha ^1,2,6, Hyejun Seo ^1,4, Jaehun Oh ^1,2,6, Byoung-Jun Kim ¹, Bum-Joon Kim ^1,2,3,4,5,6; Journal of Microbiology 2023;61(1):121-129.
DOI: https://doi.org/10.1007/s12275-022-00009-1
Published online: January 31, 2023

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 Korea¹Department 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

Corresponding author: Bum-Joon Kim ,

Received: 23 June 2022 • Revised: 20 October 2022 • Accepted: 25 November 2022

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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.

Keywords: Dhh1;Dhh1-Puf6 interaction;Fus3 MAP kinase;Phosphorylation;Ste12 expression;TPK2 kinase

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Mycobacterium paragordonae: Insights into its Research Progress and Potential Applications
Hyejun Seo, Ju-Young Lee, Bum-Joon Kim
Journal of Bacteriology and Virology.2024; 54(4): 273. CrossRef
Protection against tuberculosis achieved by dissolving microneedle patches loaded with live Mycobacterium paragordonae in a BCG prime-boost strategy
Mi-Hyun Lee, Hyejun Seo, Moon-Su Lee, Byoung Jun Kim, Hye Lin Kim, Du Hyung Lee, Jaehun Oh, Ju Yeop Shin, Ju Young Jin, Do Hyeon Jeong, Bum-Joon Kim
Frontiers in Immunology.2023;[Epub] CrossRef

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Potential Use of Mycobacterium paragordonae for Antimycobacterial Drug Screening Systems

J. Microbiol. 2023;61(1):121-129. Published online January 31, 2023

DOI: https://doi.org/10.1007/s12275-022-00009-1

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