Reactive oxygen species do not contribute to ObgE∗-mediated programmed cell death

Abstract

Programmed cell death (PCD) in bacteria is considered an important target for developing novel antimicrobials. Development of PCD-specific therapies requires a deeper understanding of what drives this process. We recently discovered a new mode of PCD in Escherichia coli that is triggered by expression of a mutant isoform of the essential ObgE protein, ObgE∗. Our previous findings demonstrate that ObgE∗-mediated cell death shares key characteristics with apoptosis in eukaryotic cells. It is well-known that reactive oxygen species (ROS) are formed during PCD in eukaryotes and play a pivotal role as signaling molecules in the progression of apoptosis. Therefore, we explored a possible role for ROS in bacterial killing by ObgE∗. Using fluorescent probes and genetic reporters, we found that expression of ObgE∗ induces formation of ROS. Neutralizing ROS by chemical scavenging or by overproduction of ROS-neutralizing enzymes did not influence toxicity of ObgE∗. Moreover, expression of ObgE∗ under anaerobic conditions proved to be as detrimental to bacterial viability as expression under aerobic conditions. In conclusion, ROS are byproducts of ObgE∗ expression that do not play a role in the execution or progression of ObgE∗-mediated PCD. Targeted therapies should therefore look to exploit other aspects of ObgE∗-mediated PCD.