ROS-Mediated Signalling in Bacteria: Zinc-Containing Cys-X-X-Cys Redox Centres and Iron-Based Oxidative Stress

Abstract

Bacteria are permanently in contact with reactive oxygen species (ROS), both over the course of their life cycle as well that present in their environment. These species cause damage to proteins, lipids, and nucleotides, negatively impacting the organism. To detect these ROS molecules and to stimulate the expression of proteins involved in antioxidative stress response, bacteria use a number of different protein-based regulatory and sensory systems. ROS-based stress detection mechanisms induce posttranslational modifications, resulting in overall conformational and structural changes within sensory proteins. The subsequent structural rearrangements result in changes of protein activity, which lead to regulated and appropriate response on the transcriptional level. Many bacterial enzymes and regulatory proteins possess a conserved signature, the zinc-containing redox centre Cys-X-X-Cys in which a disulfide bridge is formed upon oxidative stress. Other metal-dependent oxidative modifications of amino acid side-chains (dityrosines, 2-oxo-histidines, or carbonylation) also modulate the activity of redox-sensitive proteins. Using molecular biology, biochemistry, biophysical, and structure biology tools, molecular mechanisms involved in sensing and response to oxidative stress have been elucidated in detail. In this review, we analyze some examples of bacterial redox-sensing proteins involved in antioxidative stress response and focus further on the currently known molecular mechanism of function.

Zinc enhances adiponectin oligomerization to octadecamers but decreases the rate of disulfide bond formation

“…In enzymes and signaling proteins found in both prokaryotes and eukaryotes, zinc-binding cysteine-rich regions often serve as sensors of oxidative stress with zinc functioning to inhibit oxidation of key cysteine residues (Maret 2006;Paget and Buttner 2003;Wilcox et al 2001). As is the case with adiponectin in which zinc could slow down disulfide formation but could not prevent it, the thiols coordinating zinc in these zinc-containing redox sensors undergo oxidation resulting in the release of zinc ions (Bonham and Vacratsis 2009;Maret 2006;Ortiz de Orué Lucana et al 2012;Wilcox et al 2001).…”

Proteomics analysis of Listeria monocytogenes ATCC 19115 in response to simultaneous triple stresses

“…Oxidative stress is defined as interference in the balance between the production of reactive oxygen species (ROS), including free radicals, oxides and peroxides, and the ability of biological systems to readily detect their presence and detoxify ROS or repair the resulting damage (Ortiz de Orue Lucana et al 2012). In our study, two proteins with high expression levels were identified as catalase (Cat) and superoxide dismutase (Sod), which are the members of antioxidative defense system related to the ROS regulation.…”

Two distinct mechanisms of transcriptional regulation by the redox sensor YodB

“…For bacteria, the thiol groups of cysteines in proteins are commonly used as thiol-based switches in redox-sensing regulators to activate specific detoxification pathways and restore the redox balance (1)(2)(3). Direct sensing and quick responses by transcription factors are regarded as an efficient way to promote the survival of a tiny bacterium and overcome oxidation stress (1)(2)(3). In addition, the redox signaling pathways have also been used as important virulence regulators that allow pathogenic bacteria to adapt to the host immune defense system (4).…”