Copper-Mediated Antimicrobial Activity : Targeting Cytochrome c Complexes Across Bacterial Species
- 1CNRS
Abstract
Copper (Cu) exerts potent antibacterial activity and contributes to mammalian immune defense. Although solvent exposed 4Fe-4S clusters in cytoplasmic dehydrogenases are major intracellular targets of Cu, its chemical reactivity and subcellular distribution suggest that additional cellular processes may be vulnerable to Cu toxicity. Here, we identify c-type cytochrome biogenesis as a conserved target of Cu excess across diverse pathogenic and environmental bacteria. Analysis of respiratory membrane complexes from pathogens, including Vibrio cholerae and Pseudomonas aeruginosa, revealed pronounced and selective sensitivity of c-type cytochrome-containing complexes to excess Cu. In P. aeruginosa, elevated Cu impaired the cbb3-type cytochrome c oxidase and NapBC-containing cytochrome c complexes while largely sparing complexes independent of c-type cytochromes, including the aa3-type cytochrome c oxidase and succinate dehydrogenase. In contrast, the caa3-type cytochrome c oxidase of Bacillus subtilis, which contains a covalently bound cytochrome c subunit, was also severely affected. Cu likewise depleted c-type cytochromes in plant-associated and photosynthetic bacteria, indicating that this vulnerability is broadly conserved. Complementary analyses in B. subtilis and Escherichia coli showed that Cu primarily disrupts c-type cytochrome assembly rather than promoting the degradation of preassembled complexes. These findings establish c-type cytochrome-containing respiratory complexes as conserved targets of Cu toxicity. Given their central role in electron transport and adaptation to oxygen-limited environments, disruption of cytochrome c biogenesis may contribute to Cu antimicrobial activity and expose a potential vulnerability in pathogens that rely on c-type cytochromes for microaerobic respiration and colonization of hypoxic host tissues.
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BibTeX
@misc{durand2026coppermediated,
title = {{Copper-Mediated Antimicrobial Activity : Targeting Cytochrome c Complexes Across Bacterial Species}},
author = {A. Durand and A.-S. Steunou and M. A. Khan and M.-L. Bourbon and C. Cassier-Chauvat and F. Chauvat and S. Ouchane},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.17.759849},
url = {https://www.biorxiv.org/content/10.64898/2026.10.17.759849v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Copper-Mediated Antimicrobial Activity : Targeting Cytochrome c Complexes Across Bacterial Species
AU - A. Durand
AU - A.-S. Steunou
AU - M. A. Khan
AU - M.-L. Bourbon
AU - C. Cassier-Chauvat
AU - F. Chauvat
AU - S. Ouchane
PY - 2026
DA - 2026/10/17
PB - bioRxiv
DO - 10.64898/2026.10.17.759849
UR - https://www.biorxiv.org/content/10.64898/2026.10.17.759849v1
AB - Copper (Cu) exerts potent antibacterial activity and contributes to mammalian immune defense. Although solvent exposed 4Fe-4S clusters in cytoplasmic dehydrogenases are major intracellular targets of Cu, its chemical reactivity and subcellular distribution suggest that additional cellular processes may be vulnerable to Cu toxicity. Here, we identify c-type cytochrome biogenesis as a conserved target of Cu excess across diverse pathogenic and environmental bacteria. Analysis of respiratory membrane complexes from pathogens, including Vibrio cholerae and Pseudomonas aeruginosa, revealed pronounced and selective sensitivity of c-type cytochrome-containing complexes to excess Cu. In P. aeruginosa, elevated Cu impaired the cbb3-type cytochrome c oxidase and NapBC-containing cytochrome c complexes while largely sparing complexes independent of c-type cytochromes, including the aa3-type cytochrome c oxidase and succinate dehydrogenase. In contrast, the caa3-type cytochrome c oxidase of Bacillus subtilis, which contains a covalently bound cytochrome c subunit, was also severely affected. Cu likewise depleted c-type cytochromes in plant-associated and photosynthetic bacteria, indicating that this vulnerability is broadly conserved. Complementary analyses in B. subtilis and Escherichia coli showed that Cu primarily disrupts c-type cytochrome assembly rather than promoting the degradation of preassembled complexes. These findings establish c-type cytochrome-containing respiratory complexes as conserved targets of Cu toxicity. Given their central role in electron transport and adaptation to oxygen-limited environments, disruption of cytochrome c biogenesis may contribute to Cu antimicrobial activity and expose a potential vulnerability in pathogens that rely on c-type cytochromes for microaerobic respiration and colonization of hypoxic host tissues.
ER -