Adaptation to oxidative stress by Gram-positive bacteria: the redox sensing system HbpS-SenS-SenR from Streptomyces reticuli

In common with all other living organisms, Gram-positive bacteria must continuously deal with stress situations in vivo. Such stress conditions may include changes in environmental temperature, pH, humidity, etc. In the case of many pathogens including Mycobacterium tuberculosis, Staphylococcus aureus, Corynebacterium diphtherieae, Enterococcus phaecalis, Streptococcus pneumoniae or Bacillus anthracis such changes include an efficient response to changing environments during both infection and virulence within the host. Other non-pathogenic and soil-dwelling bacteria, such as Streptomyces reticuli, Bacillus subtillis, Corynebacterium glutamicum or Mycobacterium snegmatis, must also respond to a wide variety of environmental stimuli including, UV-radiation or nutritional stress. All these bacteria have developed sensory systems that facilitate adaptation to changes in the environmental conditions. Recently, the three-component signalling system HbpS-SenS-SenR from the cellulose degrader Streptomyces reticuli has been reported as an example of a redox sensing pathway in bacteria. Using a combination of structural biology and in vivo and in vitro experiments it was demonstrated that the extracellular oligomer-forming protein HbpS acts in concert with the two-component system SenSSenR in the sensing and reaction of the bacteria to hemeand iron-mediated oxidative stress. HbpS can bind and degrade heme via a non-enzymatic pathway known as coupled oxidation and it has been proposed that HbpS communicates the extracellular presence of heme and oxidative stress to the bacteria through the membrane-embedded sensor histidine kinase SenS using HbpS-bound iron ions. SenS subsequently phosphorylates the response regulator SenR, acting as a transcriptional regulator of a number of genes encoding for redox active proteins that are involved in the adaptation of the bacteria to oxidative stress. In this report, we analyze the sensing of signals by Gram-positive bacteria upon oxidative stress. We also focus further on the HbpS-SenS-SenR system and provide new insights into molecular mechanism used by Gram-positive bacteria to monitor and react to changes in environmental conditions. A knowledge of the interaction and reaction of bacteria to changes in their environment will open new avenues of understanding that could have many applications in fields as diverse as agriculture, biotechnology, ecosystem monitoring as well as human medicine.