Frontiers in Microbiology (Aug 2021)
Rufomycin Exhibits Dual Effects Against Mycobacterium abscessus Infection by Inducing Host Defense and Antimicrobial Activities
- Cho Rong Park,
- Cho Rong Park,
- Cho Rong Park,
- Seungwha Paik,
- Young Jae Kim,
- Young Jae Kim,
- Young Jae Kim,
- Jin Kyung Kim,
- Jin Kyung Kim,
- Sang Min Jeon,
- Sang Min Jeon,
- Sang Min Jeon,
- Sang-Hee Lee,
- Jake Whang,
- Jinhua Cheng,
- Joo-Won Suh,
- Jin Cao,
- Jin Cao,
- Gauri Shetye,
- Gauri Shetye,
- Shao-Nong Chen,
- James McAlpine,
- Guido F. Pauli,
- Scott Franzblau,
- Scott Franzblau,
- Sanghyun Cho,
- Sanghyun Cho,
- Eun-Kyeong Jo,
- Eun-Kyeong Jo,
- Eun-Kyeong Jo
Affiliations
- Cho Rong Park
- Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
- Cho Rong Park
- Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea
- Cho Rong Park
- Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea
- Seungwha Paik
- Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
- Young Jae Kim
- Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
- Young Jae Kim
- Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea
- Young Jae Kim
- Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea
- Jin Kyung Kim
- Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
- Jin Kyung Kim
- Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea
- Sang Min Jeon
- Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
- Sang Min Jeon
- Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea
- Sang Min Jeon
- Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea
- Sang-Hee Lee
- Center for Research Equipment, Korea Basic Science Institute, Cheongju, South Korea
- Jake Whang
- Korea Mycobacterium Resource Center & Basic Research Section, The Korean Institute of Tuberculosis, Cheongju, South Korea
- Jinhua Cheng
- Myongji Bioefficacy Research Center, Myongji University, Yongin, South Korea
- Joo-Won Suh
- Myongji Bioefficacy Research Center, Myongji University, Yongin, South Korea
- Jin Cao
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Jin Cao
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Gauri Shetye
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Gauri Shetye
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Shao-Nong Chen
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- James McAlpine
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Guido F. Pauli
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Scott Franzblau
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Scott Franzblau
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Sanghyun Cho
- Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Sanghyun Cho
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, United States
- Eun-Kyeong Jo
- Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
- Eun-Kyeong Jo
- Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea
- Eun-Kyeong Jo
- Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea
- DOI
- https://doi.org/10.3389/fmicb.2021.695024
- Journal volume & issue
-
Vol. 12
Abstract
Nontuberculous mycobacterial pulmonary infection is often aggravated due to antibiotic resistance issues. There is a need for development of new drugs inducing both host immune responses and antimicrobial activities. This study shows that the rufomycins 4/5/6/7 (Rufomycin 4–7), which targets ClpC1 as a subunit of caseinolytic protein complex ClpC1/ClpP1/ClpP2 of mycobacteria, exhibits a dual effect in host innate defense and in vivo antimicrobial activities against a rough morphotype of Mycobacterium abscessus (Mabs-R), a clinically severe morphotype that causes hyperinflammation. Rufomycin 4–7 treatment showed antimicrobial effects against Mabs pulmonary infection in vivo and in macrophages. In addition, Rufomycin 4–7 significantly decreased inflammation, but enhanced the autophagy/lysosomal genes through upregulation of the nuclear translocation of transcription factor EB (TFEB). Furthermore, Rufomycin 4–7 treatment effectively inhibited mitochondrial damage and oxidative stresses in macrophages during Mabs-R infection. Collectively, Rufomycin 4–7-mediated dual effects inducing both antimicrobial activities and host immune defense might confer an advantage to treatment against Mabs-R infection.
Keywords
