Heme in Bacterial Pathogenesis and as an Antimicrobial Target
Peiyi Chen, Eric P. Skaar
Abstract
Heme is an essential molecule required for critical biochemical processes in most vertebrates and bacteria. During infections, vertebrate hosts sequester heme away from invading pathogens, a process known as nutritional immunity, driving bacteria to evolve diverse mechanisms to evade this immunity and cause diseases. This review explores the functions of heme at the host-pathogen interface. We discuss the multifaceted roles of heme in bacterial pathogenesis and the potential for heme-targeting antimicrobial therapies. Beyond serving as a source of iron in the host environment, where iron bioavailability is limited, heme contributes to the structural stability and enzymatic functions of hemoproteins. We examine the regulatory mechanisms governing bacterial heme homeostasis in the host environment including sensing, detoxification, acquisition, utilization, and degradation pathways. Understanding how heme influences bacterial survival and virulence can lead to the development of novel therapeutic strategies that target the various essential and conserved mechanisms of heme homeostasis in bacterial pathogens. Given the rising challenge of antibiotic resistance, heme-based therapeutic interventions are promising strategies for the treatment of bacterial infections.