Abstract
Pathogenic bacteria acquire transition metals for cell viability and persistence of infection in competition with host nutritional defenses. The human host employs a variety of mechanisms to stress the invading pathogen with both cytotoxic metal ions and oxidative and nitrosative insults while withholding essential transition metals from the bacterium. For example, the S100 family protein calprotectin (CP) found in neutrophils is a calcium-activated chelator of extracellular Mn and Zn and is found in tissue abscesses at sites of infection by Staphylococcus aureus. In an adaptive response, bacteria have evolved systems to acquire the metals in the face of this competition while effluxing excess or toxic metals to maintain a bioavailability of transition metals that is consistent with a particular inorganic “fingerprint” under the prevailing conditions. This review highlights recent biological, chemical and structural studies focused on manganese (Mn) acquisition and homeostasis and connects this process to oxidative stress resistance and iron (Fe) availability that operates at the human host-pathogen interface.
Highlights
The most abundant transition metals in humans are iron (Fe) and zinc (Zn) and it is generally accepted that a clinical deficiency in host levels of either metal increases the incidence of infectious disease and mortality (Haider and Bhutta, 2009; Kumar and Choudhry, 2010; Lassi et al, 2010)
This review summarizes recent work in the area of “Mn-centric” nutritional immunity (Weinberg, 1975) placed in the context of the inorganic physiology of the cell and the “fight over metals” implied by recent studies of Mn speciation and chemistries of low molecular weight (LMW) Mn complexes (McNaughton et al, 2010; Barnese et al, 2012; Sharma et al, 2013), and the structures and metal binding affinities of the bacterial high affinity import systems for Mn relative to the extracellular antibacterial protein calprotectin (Corbin et al, 2008; Damo et al, 2013; Hayden et al, 2013)
The discovery of host immune proteins that limit biologically available Mn(II) for both intracellular and extracellular pathogens in an effort to cripple the resistance of invading pathogens to reactive oxygen species (ROS) establishes this as a general strategy used by the host to curtail bacterial infections (Corbin et al, 2008; Damo et al, 2013; Kehl-Fie et al, 2013)
Summary
Pathogenic bacteria acquire transition metals for cell viability and persistence of infection in competition with host nutritional defenses. The human host employs a variety of mechanisms to stress the invading pathogen with both cytotoxic metal ions and oxidative and nitrosative insults while withholding essential transition metals from the bacterium. Bacteria have evolved systems to acquire the metals in the face of this competition while effluxing excess or toxic metals to maintain a bioavailability of transition metals that is consistent with a particular inorganic “fingerprint” under the prevailing conditions. This review highlights recent biological, chemical and structural studies focused on manganese (Mn) acquisition and homeostasis and connects this process to oxidative stress resistance and iron (Fe) availability that operates at the human host-pathogen interface
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