Streamlining of defenses against copper makes host-restricted pathogen reliant on custom-made operon

ABSTRACT: Copper is both essential and toxic to living beings, which therefore tightly control its intracellular concentration. At the host-pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in the whooping cough agent Bordetella pertussis, which lives in the human respiratory mucosa and has no environmental reservoir. B. pertussis has considerably streamlined copper homeostasis mechanisms relative to other Gram-negative bacteria. Its single remaining defense line against copper intoxication consists in a metallochaperone diverted for copper passivation and two enzymes involved in peroxide detoxification, which together fight two stresses encountered in phagolysosomes. The three proteins are encoded by an original, composite operon assembled in an environmental ancestor and which is under sensitive control by copper. Interestingly, this system appears to play a role in persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a new strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Bordetella Bronchiseptica

TISSUE(S): Cell Culture

SUBMITTER: SALIOU Jean-Michel  

LAB HEAD: Saliou Jean-Michel

PROVIDER: PXD020900 | Pride | 2021-09-09

REPOSITORIES: Pride