Rufomycin Exhibits Dual Effects Against Mycobacterium abscessus Infection by Inducing Host Defense and Antimicrobial...

Area of Science:

• Microbiology
• Immunology
• Pharmacology

Background:

• Nontuberculous mycobacterial pulmonary infections are challenging due to antibiotic resistance.
• Novel therapeutic strategies are needed to combat these infections by enhancing host immunity and antimicrobial activity.

Purpose of the Study:

• To investigate the dual therapeutic potential of rufomycins 4-7 (Rufomycin 4-7) against *Mycobacterium abscessus* rough morphotype (Mabs-R).
• To evaluate Rufomycin 4-7's impact on host innate defense mechanisms and antimicrobial efficacy.

Main Methods:

• Assessing antimicrobial effects of Rufomycin 4-7 against Mabs-R in vitro (macrophages) and in vivo (pulmonary infection model).
• Analyzing the drug's effect on inflammation, autophagy/lysosomal pathways (via TFEB translocation), and oxidative stress in infected macrophages.
• Investigating the mechanism of action targeting the mycobacterial ClpC1 subunit.

Main Results:

• Rufomycin 4-7 demonstrated antimicrobial activity against Mabs-R pulmonary infections and in macrophages.
• Treatment significantly reduced inflammation and enhanced autophagy/lysosomal gene expression by upregulating TFEB nuclear translocation.
• Rufomycin 4-7 inhibited mitochondrial damage and oxidative stress in macrophages during Mabs-R infection.

Conclusions:

• Rufomycin 4-7 exhibits a dual therapeutic effect, combining direct antimicrobial action with host immune modulation.
• This dual action offers a promising strategy for treating severe Mabs-R infections, potentially overcoming antibiotic resistance challenges.