PacL-organized membrane-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis DOI Open Access
Pierre Dupuy, Yves‐Marie Boudehen, Marion Faucher

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Metal ion homeostasis is crucial for bacterial pathogens to withstand metal-induced stress during infection. However, the mechanisms underlying resistance metal remain incompletely understood, particularly how bacteria coordinate responses simultaneous exposure multiple metals. Here, we uncover a previously unrecognized mechanism by which Mycobacterium tuberculosis , causative agent of tuberculosis, orchestrates coordinated response multi-metal stress. We demonstrate that M. assembles dynamic, membrane-associated platforms, organized PacL proteins, confer metals simultaneously. proteins function as scaffolds, clustering P-type ATPase (P-ATPase) pumps, CtpC, CtpG, and CtpV, into functional complexes term "effluxosomes". Our findings show are critical stabilizing CtpG within clusters, conferring cadmium tolerance, while CtpC serves backup, promoting cross-resistance both zinc cadmium. Using super-resolution microscopy single-particle tracking, elucidate 3D structure dynamics effluxosomes in mycobacterial membrane. further conserved residues transmembrane domain assembly dynamic effluxosomes, essential P-ATPase activity. Additionally, reveal PacL1 exhibits metallochaperone activity, binding zinc, cadmium, copper via C-terminal motif. Proximity labeling identifies an extensive interaction network, encompassing involved adaptation. introduce efflux machineries mediate providing new insights unveiling potential antimicrobial targets.

Язык: Английский

PacL-organized membrane-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis DOI Open Access
Pierre Dupuy, Yves‐Marie Boudehen, Marion Faucher

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Metal ion homeostasis is crucial for bacterial pathogens to withstand metal-induced stress during infection. However, the mechanisms underlying resistance metal remain incompletely understood, particularly how bacteria coordinate responses simultaneous exposure multiple metals. Here, we uncover a previously unrecognized mechanism by which Mycobacterium tuberculosis , causative agent of tuberculosis, orchestrates coordinated response multi-metal stress. We demonstrate that M. assembles dynamic, membrane-associated platforms, organized PacL proteins, confer metals simultaneously. proteins function as scaffolds, clustering P-type ATPase (P-ATPase) pumps, CtpC, CtpG, and CtpV, into functional complexes term "effluxosomes". Our findings show are critical stabilizing CtpG within clusters, conferring cadmium tolerance, while CtpC serves backup, promoting cross-resistance both zinc cadmium. Using super-resolution microscopy single-particle tracking, elucidate 3D structure dynamics effluxosomes in mycobacterial membrane. further conserved residues transmembrane domain assembly dynamic effluxosomes, essential P-ATPase activity. Additionally, reveal PacL1 exhibits metallochaperone activity, binding zinc, cadmium, copper via C-terminal motif. Proximity labeling identifies an extensive interaction network, encompassing involved adaptation. introduce efflux machineries mediate providing new insights unveiling potential antimicrobial targets.

Язык: Английский

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