Redox Signaling in Human Pathogens

Abstract

In recent studies of human bacterial pathogens, oxidation sensing and regulation have been shown to impact very diverse pathways that extend beyond inducing antioxidant genes in the bacteria. In fact, some redox-sensitive regulatory proteins act as major regulators of bacteria's adaptability to oxidative stress, an ability that originates from immune host response as well as antibiotic stress. Such proteins play particularly important roles in pathogenic bacteria S. aureus, P. aeruginosa, and M. tuberculosis in part because reactive oxygen species and reactive nitrogen species present significant challenges for pathogens during infection. Herein, we review recent progress toward the identification and understanding of oxidation sensing and regulation in human pathogens. The newly identified redox switches in pathogens are a focus of this review. We will cover several reactive oxygen species-sensing global regulators in both gram-positive and gram-negative pathogenic bacteria in detail. The following discussion of the mechanisms that these proteins employ to sense redox signals through covalent modification of redox active amino acid residues or associated metalloprotein centers will provide further understanding of bacteria pathogenesis, antibiotic resistance, and host-pathogen interaction.

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

“…The abrupt change of the redox status, on the other hand, is also used by the pathogen as a signal to adapt and evade the host defense. The reactive cysteine in the SarA/MgrA family proteins is known to be redox active and plays a significant role in responding to oxidative stress (40). As shown in Fig.…”

Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA

“…This metabolic burden and the concomitant oxidative stress necessitate a delicate sensing system to enable the bacterium to avoid the detrimental effects caused by agr activation. Indeed, S. aureus, as a successful human pathogen, has developed a rapid adaptive response to a sublethal dose of oxidants (4,6), thereby reorienting gene expression for antioxidation. Our discovery suggests that the agr system serves to trigger bacterial response (through activation of bsaA gene in particular) to oxidative stress through an intracellular disulfide switch contained in the response regulator AgrA.…”

Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum

“…Recently, bacilliredoxins and thioredoxins were shown to be the reducing systems for the 1-Cys OhrR from Bacillus subtilis (16) and for the 2-Cys OhrR from Chromobacterium violaceum (17), respectively. OhrR belongs to the MarR family of transcription factors, which contains many other thiol-based redox-sensing regulators that respond to ROS or to reactive electrophilic species (14,18).…”