Key players in the regulation of iron homeostasis at the host-pathogen interface

Abstract

Iron plays a crucial role in the biochemistry and development of nearly all living organisms. Iron starvation of pathogens during infection is a striking feature utilized by a host to quell infection. In mammals and some other animals, iron is essentially obtained from diet and recycled from erythrocytes. Free iron is cytotoxic and is readily available to invading pathogens. During infection, most pathogens utilize host iron for their survival. Therefore, to ensure limited free iron, the host’s natural system denies this metal in a process termed nutritional immunity. In this fierce battle for iron, hosts win over some pathogens, but others have evolved mechanisms to overdrive the host barriers. Production of siderophores, heme iron thievery, and direct binding of transferrin and lactoferrin to bacterial receptors are some of the pathogens’ successful strategies which are highlighted in this review. The intricate interplay between hosts and pathogens in iron alteration systems is crucial for understanding host defense mechanisms and pathogen virulence. This review aims to elucidate the current understanding of host and pathogen iron alteration systems and propose future research directions to enhance our knowledge in this field.

Enterobactin and Salmochelin S4 inhibit the growth ofStaphylococcus aureus

“…Specifically, during infection, the host’s innate immune system starves pathogens by reducing intestinal iron absorption. This is achieved by increasing the production of ferritin and lactoferrin by neutrophils at the sites of infection, and by producing siderocalins (Cassat and Skaar, 2013; Nairz et al, 2014; Marchetti et al, 2020; Ullah and Lang, 2023). However, microorganisms overcome this problem by developing highly efficient uptake systems for using the iron present in the host through low-molecular weight organic chelators (150 to 2000 Da) called siderophores.…”