Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

Abstract

Molecular oxygen (O 2 ) and nitric oxide (NO) are diatomic gases that play major roles in infection. The host innate immune system generates reactive oxygen species and NO as bacteriocidal agents and both require O 2 for their production. Furthermore, the ability to adapt to changes in O 2 availability is crucial for many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic bacteria have evolved transcriptional regulatory systems that perceive these gases and respond by reprogramming gene expression. Direct sensors possess iron-containing co-factors (iron-sulfur clusters, mononuclear iron, heme) or reactive cysteine thiols that react with O 2 and/or NO. Indirect sensors perceive the physiological effects of O 2 starvation. Thus, O 2 and NO act as environmental cues that trigger the coordinated expression of virulence genes and metabolic adaptations necessary for survival within a host. Here, the mechanisms of signal perception by key O 2 -and NO-responsive bacterial transcription factors and the effects on virulence gene expression are reviewed, followed by consideration of these aspects of gene regulation in two major pathogens, Staphylococcus aureus and Mycobacterium tuberculosis.

Dialogue between E. coli free radical pathways and the mitochondria of C. elegans

“…Reactive oxygen is generated by animal innate immune systems in a bacterial infection (49). The E. coli electron transport mutations that induce bacterial response pathways such as the SoxRS and OxyR pathways may mimic E. coli in its pathogenic state in an infection, where ROS is an indication of an animal immune response.…”

What a difference a cluster makes: The multifaceted roles of IscR in gene regulation and DNA recognition

“…Pathogenic bacteria have evolved transcriptional regulatory systems that perceive such hostile conditions and respond by reprogramming gene expression [7,8]. Defensive mechanisms that detoxify ROS and RNS and repair damaged cell components essential for the intracellular survival of the pathogen during infection are strictly regulated in pathogens [7,71].…”

“…Pathogenic bacteria rely on transcriptional regulatory systems to perceive such hostile conditions during host invasion and respond by reprogramming gene expression [7,8]. It has been recently shown that IscR functions as virulence factor in several pathogenic bacteria, modulating gene expression for an adequate response to the stress conditions at the host-pathogen interface [9][10][11][12].…”

The emerging role of gasotransmitters in the pathogenesis of tuberculosis

“…Instead, Mtb uses two distinct redox couples, mycothiol and ergothioneine, and harbors at least 50 proteins containing Fe–S clusters that facilitate an intercellular life cycle [37, 175]. Interestingly, Mtb has a higher incidence of Fe–S cluster proteins (~6.5 motifs/1000 ORFs) than other aerobic bacteria (2.8 motifs/1000 ORFs), underscoring the importance of Fe–S cluster proteins to pathogenic adaptations of Mtb [176, 177].…”