Work

The Antibiotic-Resistant Protein MfpA Modulates Host Cell Apoptosis and Promotes Mycobacterial Survival by Targeting Mitochondria and Regulating the NF-κB Signaling Pathway

Year: 2025

Type: article

Abstract: Mycobacterium tuberculosis (Mtb) is a major global health threat, exacerbated by the emergence of antibiotic-resistant strains. This study investigated fluoroquinolone resistance protein A (MfpA), which enhances mycobacterial survival by targeting host mitochondria and regulating apoptosis. Wild-type (WT) and knockout (KO) Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strains, a common model for Mtb, were utilized to examine host cell responses. Compared to WT strains, KO strains showed reduced colony-forming units (CFUs), elevated TNF-α and IL-6 levels, and increased apoptosis. MfpA was found to localize to mitochondria, increasing ROS production and disrupting mitochondrial membrane potential. Transcriptomic analysis revealed that MfpA modulated the NF-κB signaling pathway, regulating the expression of gadd45β. These results suggest that MfpA drives both antibiotic resistance and virulence by suppressing apoptosis via the mitochondrial and NF-κB pathways, promoting mycobacterial persistence. Studies using BCG provide valuable insight into Mtb’s survival mechanisms, highlighting MfpA’s dual role in resistance and pathogenesis.

Source: Cells

DOI: 10.3390/cells14120867

Authors: Weishan Zhang, Zheng Jiang, Kaixia Mi

Institutions: Chinese Academy of Sciences, Institute of Microbiology, University of Chinese Academy of Sciences

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258