New roles for amino acid pathways in subverting metal stress in Streptococcus

Transition metals such as copper (Cu) and zinc (Zn) are important trace elements required for a variety of cellular functions in bacteria and higher organisms.

When present in excess, these highly reactive elements can intoxicate bacteria and are used by the mammalian host as a mechanism to kill invading pathogens.

Discrete genetic systems for Cu and Zn homeostasis are described in several bacterial pathogens, including in streptococci, comprising metal import and export proteins controlled by their cognate transcriptional regulators.

Little is known about how bacterial metabolic pathways contribute to surviving metal intoxication, an area of emerging importance in the field of nutritional immunity.

This project builds on strong foundational work by the investigator, Dr Sullivan, to investigate roles for amino acid and nitrogen assimilation pathways in supporting resistance to metal intoxication.

The study focuses on Group B streptococcus, the leading cause of bacterial neonatal infections and an emergent pathogen of invasive disease in non-pregnant adults.

Using forefront molecular genetic technologies, the project will establish a new fundamental understanding of how bacteria can resist killing by Cu and Zn, a process that occurs at the host-pathogen interface.

The mechanisms highlighted in the preliminary data hint at biological processes that are likely to be broadly applicable to a range of human pathogens of critical importance.

Targeting this highly novel information in future studies may lead to new ways in which bacteria can be eliminated using treatment strategies that do not rely on over-used antibiotics in a world of ever-increasing antimicrobial resistance.