Neisseria gonorrhoeae Exposed to Sublethal Levels of Hydrogen Peroxide Mounts a Complex Transcriptional Response

Neisseria gonorrhoeae mounts a substantial transcriptional program in response to hydrogen peroxide (HP), a prominent reactive oxygen species (ROS) encountered during infection. We tested which strain FA1090 genes show differential transcript abundance in response to sublethal amounts of HP to differentiate HP-responsive signaling from widespread cellular death and dysregulation. RNA sequencing (RNA-Seq) revealed that 150 genes were significantly upregulated and 143 genes downregulated following HP exposure. We annotated HP-responsive operons and all transcriptional start sites (TSSs) and identified which TSSs responded to HP treatment. We compared the HP responses and other previously reported genes and found only partial overlapping of other regulatory networks, indicating that the response to HP involves multiple biological functions. Using a representative subset of responsive genes, we validated the RNA-Seq results and found that the HP transcriptome was similar to that of sublethal organic peroxide. None of the genes in the representative subset, however, responded to sublethal levels of HOCl or O-2(-). These results support the idea that N. gonorrhoeae may use variations in HP levels as a signal for different stages of infection. IMPORTANCE The strict human pathogen Neisseria gonorrhoeae is the only causative agent of the sexually transmitted disease gonorrhea. This bacterium encounters hydrogen peroxide produced from host cells during infection, but the organism survives in the presence of this antimicrobial agent. This work shows that the bacterium responds to hydrogen peroxide by regulating the expression of many genes involved in multiple processes.