Streamlined copper defenses make Bordetella pertussis reliant on custom-made operon

Alex Rivera-Millot,Jonathan Chatagnon,Françoise Jacob-Dubuisson,Gauthier Roy,Jean-Michel Saliou,Stéphanie Slupek,Sophie Salomé-Desnoulez,David Hot,Gabriel Billon,Véronique Alaimo,Rudy Antoine,Camille Locht

doi:10.1038/s42003-020-01580-2

Abstract

Copper is both essential and toxic to living beings, which tightly controls its intracellular concentration. At the host–pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in 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 consists of a metallochaperone diverted for copper passivation, CopZ, and two peroxide detoxification enzymes, PrxGrx and GorB, which together fight stresses encountered in phagocytic cells. Those proteins are encoded by an original, composite operon assembled in an environmental ancestor, which is under sensitive control by copper. This system appears to contribute to persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.

Highlights

Copper is both essential and toxic to living beings, which tightly controls its intracellular concentration
Cu-treated B. pertussis started growing at the same rate as the untreated culture, suggesting that copper has a bacteriostatic effect, whereas growth of Cu-treated B. bronchiseptica started at the same time as the control but at a slower pace, indicating a rapid adaptation to copper-rich conditions
This was confirmed by the observation that the addition of fresh ascorbate after a few hours to B. pertussis cultured in the presence of 5 mM copper prevented bacterial growth (Supplementary Figure S1)

Summary

Introduction

Copper is both essential and toxic to living beings, which tightly controls its intracellular concentration. Its single remaining defense line consists of a metallochaperone diverted for copper passivation, CopZ, and two peroxide detoxification enzymes, PrxGrx and GorB, which together fight stresses encountered in phagocytic cells. Those proteins are encoded by an original, composite operon assembled in an environmental ancestor, which is under sensitive control by copper. Eukaryotic organisms take advantage of copper toxicity to kill invading microorganisms[8,9] Predatory protists, such as amoebae, and phagocytic cells of higher eukaryotes import copper for bactericidal purposes[10,11]. Its only line of defense consists of an original operon to withstand copper excess and peroxides, both encountered in phagocytic cells

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Conclusion