Metal manipulators and regulators in human pathogens: A comprehensive review on microbial redox copper metalloenzymes "multicopper oxidases and superoxide dismutases"

Abstract

The chemistry of metal ions with human pathogens is essential for their survival, energy generation, redox signaling, and niche dominance. To regulate and manipulate the metal ions, various enzymes and metal chelators are present in pathogenic bacteria. Metalloenzymes incorporate transition metal such as iron, zinc, cobalt, and copper in their reaction centers to perform essential metabolic functions; however, iron and copper have gained more importance. Multicopper oxidases have the ability to perform redox reaction on phenolic substrates with the help of copper ions. They have been reported from Enterobacteriaceae, namely Salmonella enterica, Escherichia coli, and Yersinia enterocolitica, but their role in virulence is still poorly understood. Similarly, superoxide dismutases participate in reducing oxidative stress and allow the survival of pathogens. Their role in virulence and survival is well established in Salmonella typhimurium and Mycobacterium tuberculosis. Further, to ensure survival against stress, like metal starvation or metal toxicity, redox metalloenzymes and metal transportation systems of pathogens actively participate in metal homeostasis. Recently, the omics and protein structure biology studies have helped to predict new targets for regulation the colonization potential of the pathogenic strains. The current review is focused on the major roles of redox metalloenzymes, especially MCOs and SODs of human pathogenic bacteria.

Keywords: Gut microbiota; Laccase; Metalloenzymes; Multicopper oxidase; Redox reaction; Superoxide dismutase.