Bacterial copper handling: Opportunities for antimicrobial development

Trace nutrient metal ions (iron, manganese, zinc, copper) are essential for the function of nearly half of all proteins but they are toxic to cells if present in excess or if inserted into the wrong sites. The battle to control metal availability is a key component of host-pathogen interactions in so-called "Nutritional Immunity", and there is growing interest in developing agents that manipulate nutrient metal level and location as new antimicrobial therapeutics.

It has recently emerged that host innate immune cells use copper to kill invading bacteria. To avoid copper stress, most bacteria possess copper tolerance genes that encode an array of proteins for efflux, trafficking (chaperones), and storage. These genes contribute to bacterial virulence, and they are usually transcriptionally controlled by a copper sensor. Extensive in silico searches have identified Neisseria sp. (N. gonorrhoeae is listed by the WHO amongst the highest priority global pathogens) as one exception to this dogma. A recognisable copper sensor is missing from this organism and there is no identifiable system for copper homeostasis. Instead, several genes encoding putative and established cuproproteins (including a copper efflux pump) are scattered throughout the genome but their roles in copper tolerance are largely untested.

We hypothesise that Neisseria employs novel mechanisms for copper tolerance that have not been described previously in other bacteria. The student will identify and characterise components of this system using cross-disciplinary methods across the biosciences.