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Role of metals and the cellular redox states in host-pathogen interactions

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Adaptation to changes in redox conditions is essential for the survival of cells. Unicellular pathogenic organisms are appropriate model systems to study the fundamental aspects of their adaptation to the redox changes during their encounter with the host. In Prokaryotes, changes in the redox state elicit ...

Adaptation to changes in redox conditions is essential for the survival of cells. Unicellular pathogenic organisms are appropriate model systems to study the fundamental aspects of their adaptation to the redox changes during their encounter with the host. In Prokaryotes, changes in the redox state elicit alterations in the transcriptional and translational landscapes. Often, metals are critical sensors that coordinate the response to changes in redox conditions. Metals serve as cofactors for DNA binding transcription factors, cofactors for the protein synthesis machinery, and as sensors within two component signal transduction systems (TCS). Changes in the redox state of metal cofactors cause changes in the expression or translation of genetic factors, which lead to changes in the ability of the cell to survive the changes. Because of the reactivity of transition metals with oxygen and its partially reduced intermediates (i.e., O2-, H2O2, and HO.) there is an intimate connection between the function of metals and the adaptation to fluctuating oxygen concentrations. In addition to oxygen, other reactive molecules such as nitric oxide (NO.) are capable of disrupting the metal cofactor of redox sensing proteins. Reactive oxygen and nitrogen species (ROS and RNS) are key molecules produced by the innate arm of host immune cells. In addition, increasing evidence indicates that innate cells manipulate the availability of transition metals to inhibit the survival of bacterial pathogens. Therefore, increasing the exposure of bacteria to ROS and RNS can coincide with fluctuations in the metal content. However, pathogens have multiple mechanisms to adapt to the changing redox state within the host. Both animal and plant pathogens have similar mechanisms of metal acquisition and redox sensing leading to adaptation to the changing environment, suggesting that selective pressure has favored a common evolutionary solution to this problem. This research topic focuses on the contribution of redox sensing metals such as iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), and thiol-based sensors that serve as molecular “switches” in response to changes in the redox state in the host during infections.


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