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Review
. 2021 Apr:61:170-178.
doi: 10.1016/j.cbpa.2021.01.015. Epub 2021 Mar 11.

Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy

Ryan L Gonciarz  1 , Adam R Renslo  2
Affiliations
Review

Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy

Ryan L Gonciarz et al. Curr Opin Chem Biol. 2021 Apr.

Abstract

Chemical tools capable of detecting ferrous iron with oxidation-state specificity have only recently become available. Coincident with this development in chemical biology has been increased study and appreciation for the importance of ferrous iron during infection and more generally in host-pathogen interaction. Some of the recent findings are surprising and challenge long-standing assumptions about bacterial iron homeostasis and the innate immune response to infection. Here, we review these recent developments and their implications for antibacterial therapy.

Keywords: Activity-based probes; Anti-infectives; Antibacterial agents; Gram-negative bacteria; Host–pathogen interaction; Iron metabolism; Iron speciation; Labile iron pool; Reactivity-based probes.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adam Renslo is a co-founder and holds equity in Tatara Therapeutics, Inc.

Figures

Figure 1.
Figure 1.
Overview of iron acquisition, storage, and transport in Gram-negative bacteria with an emphasis on mechanisms of ferrous iron (Fe2+) uptake and mobilization from ferric (Fe3+) forms. The figure summarizes recent findings from studies conducted in more than one species of Gram-negative bacteria.
Figure 2.
Figure 2.
Iron and other metal ions during host-pathogen interaction. (a) Competition for Fe3+ resources is centered around bacterial siderophores and mammalian Fe3+ and siderophore-binding proteins. (b) Calprotectin (CP) is a general metal sequestering protein the binds Fe2+ and other divalent metal ions in the extracellular environment.
Figure 3.
Figure 3.
New tools to study ferrous iron in vitro and in vivo. (a) RhoNox-family probes are activated by reduction of an N-oxide bond; (b) TRX-based probes are activated by reduction of a hindered peroxide bond; (c) The probe ICL-1 releases D-aminoluciferin and can be used in luciferin-expressing cells and animals; (d) mice infected with A. baumannii show elevated Fe2+ as detected with ICL-1; (e) the drug conjugate TRX-PF508 releases an LpxC inhibitor upon sensing Fe2+ in vivo and is efficacious in an acute P. aeruginosa lung infection model.
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