Copper homeostasis in a host restricted pathogen,Bordetella pertussis

Dr. Françoise JACOB-DUBUISSON

Center for Infection and Immunity, Pasteur Institute of Lille, LILLE, France

Copper is an essential transition metal whose redox properties are used for various enzymatic oxido-reductions and in electron transfer chains. It is also toxic to living beings, and therefore its cellular concentration must be strictly controlled. Copper is part of the host-pathogen interface, as phagocytic cells actively import it to kill invading bacteria. We have investigated copper homeostasis in the whooping cough agent Bordetella pertussis, which lives in the respiratory mucosa of humans and has no known environmental reservoir. Our studies have revealed that B. pertussis has considerably streamlined its defense against copper relative to other Gram-negative bacteria. Its major line of defense consists of a custom-made operon to withstand copper excess and reactive oxygen species, both encountered in phagocytic cells. Regulation of this operon by copper is highly sensitive and with a large dynamic range. Combining responses to two types of stress found in the same environment in a single operon optimizes survival at minimal expenditure. Extensive analyses of beta proteobacterial genomes have shown a trend toward elimination of copper defense genes in the course of bacterial adaptation to eukaryotic hosts niches.