H2S and reactive sulfur signaling at the host-bacterial pathogen interface

Abstract

Bacterial pathogens that cause invasive disease in the vertebrate host must adapt to host efforts to cripple their viability. Major host insults are reactive oxygen and reactive nitrogen species as well as cellular stress induced by antibiotics. Hydrogen sulfide (H₂S) is emerging as an important player in cytoprotection against these stressors, which may well be attributed to downstream more oxidized sulfur species termed reactive sulfur species (RSS). In this review, we summarize recent work that suggests that H₂S/RSS impacts bacterial survival in infected cells and animals. We discuss the mechanisms of biogenesis and clearance of RSS in the context of a bacterial H₂S/RSS homeostasis model and the bacterial transcriptional regulatory proteins that act as "sensors" of cellular RSS that maintain H₂S/RSS homeostasis. In addition, we cover fluorescence imaging- and MS-based approaches used to detect and quantify RSS in bacterial cells. Last, we discuss proteome persulfidation (S-sulfuration) as a potential mediator of H₂S/RSS signaling in bacteria in the context of the writer-reader-eraser paradigm, and progress toward ascribing regulatory significance to this widespread post-translational modification.

Keywords: S-sulfuration; antibiotic resistance; antibiotics; cysteine; host-pathogen interface; hydrogen sulfide; microbial pathogenesis; microbiology; persulfidation; persulfide; post-translational modification (PTM); proteomics; reactive sulfur species; sulfhydryl; thiol chemistry.