MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore

authored by

Shawn C. Massoni, Nicola J. Evans, Ingo Hantke, Colleen Fenton, James H. Torpey, Katherine M. Collins, Ewelina M. Krysztofinska, Janina H. Muench, Arjun Thapaliya, Santiago Martínez-Lumbreras, Sé Hart Ferrell, Celia Slater, Xinyue Wang, Ruth Fekade, Sandra Obwar, Siyu Yin, Alishba Vazquez, Christopher B. Prior, Kürsa Turgay, Rivka L. Isaacson, Amy H. Camp

Abstract

Bacterial protein degradation machinery consists of chaperone–protease complexes that play vital roles in bacterial growth and development and have sparked interest as novel antimicrobial targets. ClpC–ClpP (ClpCP) is one such chaperone–protease complex, recruited by adaptors to specific functions in the model bacterium Bacillus subtilis and other Gram-positive bacteria, including the pathogens Staphylococcus aureus and Mycobacterium tuberculosis. Here we have identified a new ClpCP adaptor protein, MdfA (metabolic differentiation factor A; formerly YjbA), in a genetic screen for factors that help drive B. subtilis toward metabolic dormancy during spore formation. A knockout of mdfA stimulates gene expression in the developing spore, while aberrant expression of mdfA during vegetative growth is toxic. MdfA binds directly to ClpC to induce its oligomerization and ATPase activity, and this interaction is required for the in vivo effects of mdfA. Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the M. tuberculosis ClpC1 protein where bactericidal cyclic peptides bind. Altogether, our data and that of an accompanying study by Riley and colleagues support a model in which MdfA induces ClpCP-mediated degradation of metabolic enzymes in the developing spore, helping drive it toward metabolic dormancy.

Organisation(s)

Institute of Microbiology

External Organisation(s)

Mount Holyoke College
King's College London
University of Durham
Max Planck Unit for the Science of Pathogens (MPUSP)

Type

Article

Journal

Genes and Development

Volume

39

Pages

510-523

No. of pages

14

ISSN

0890-9369

Publication date

14.03.2025

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

General Medicine

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1101/gad.352498.124 (Access: Embargoed)