Zinc (Zn) and copper (Cu) are essential for optimal innate immune function and nutritional deficiency in either metal leads to increased susceptibility to bacterial infection. Recently, the decreased survival of bacterial pathogens with impaired Cu and/or Zn detoxification systems in phagocytes and animal models of infection has been reported. Consequently, a model has emerged in which the host utilises Cu and/or Zn intoxication to reduce the intracellular survival of pathogens within phagocytes. This review describes and assesses the potential role for Cu and Zn intoxication in innate immune function and their direct bactericidal function.

Formaldehyde is the simplest of all aldehydes and is highly cytotoxic. Its use and associated dangers from environmental exposure have been well documented. Detoxification systems for formaldehyde are found throughout the biological world and they are especially important in methylotrophic bacteria, which generate this compound as part of their metabolism of methanol. Formaldehyde metabolizing systems can be divided into those dependent upon pterin cofactors, sugar phosphates and those dependent upon glutathione. The more prevalent thiol-dependent formaldehyde detoxification system is found in many bacterial pathogens, almost all of which do not metabolize methane or methanol. This review describes the endogenous and exogenous sources of formaldehyde, its toxic effects and mechanisms of detoxification. The methods of formaldehyde sensing are also described with a focus on the formaldehyde responsive transcription factors HxlR, FrmR and NmlR. Finally, the physiological relevance of detoxification systems for formaldehyde in bacterial pathogens is discussed.

Significance: Copper (Cu) is an essential trace metal nutrient in health and is increasingly recognized for its role in the control of infection. The pathogenEscherichia coliencounters host niches with mild to high acidity and elevated copper levels. Our study shows that this bacterium can alter its metabolism and harness the amino acid glutamine to suppress the effects of acid stress and copper toxicity. Given the abundance of glutamine in systemic circulation and its importance in the host immune system, our work provides a new insight into the ways in which bacterial pathogens can adapt and survive host-imposed antibacterial strategies.