Quorum-sensing regulator LsrR modulates resistance to oxidative stress by interfering with sulfate assimilation in avian pathogenic Escherichia coli

Prokaryotes and eukaryotes endogenously generate the gaseous molecule hydrogen sulfide (H 2 S), which has been identified as a novel signaling molecule. Bacterial H 2 S plays a protective role against reactive oxygen species and antibiotic-induced cellular damage. Endogenous H 2 S can be produced by the assimilation pathway of sulfate and thiosulfate in Escherichia coli . The transcription regulator LsrR influences various bacterial characteristics. The results of the present study revealed that avian pathogenic E. coli (APEC) lacking LsrR exhibited increased H 2 S production and enhanced tolerance to oxidative stress. Transcriptome sequencing revealed the upregulation of genes related to the sulfate assimilation pathway after the deletion of lsrR . Further investigation demonstrated that LsrR acts as a transcriptional repressor, binds directly to the promoter region of cysPUWAM, and interacts with both CysJ and CysN, thereby inhibiting exogenous sulfate assimilation and decreasing the oxidative stress resistance of APEC. Additionally, the absence of lsrR facilitated the survival of APEC94 in macrophage RAW264.7 cells. Our findings suggest that LsrR represses resistance to oxidative stress in APEC by interfering with the sulfate assimilation pathway and provide valuable insights into host-pathogen interactions. IMPORTANCE Avian pathogenic Escherichia coli (APEC) exhibits complex serotypes and widespread antibiotic resistance, placing a significant economic burden on the poultry industry. The LuxS/AI-2 quorum-sensing systems, which are closely associated with bacterial growth, biofilm formation, and virulence, play important regulatory roles in the virulence of E. coli (including avian pathogenic E. coli , serotype O 78 ) by regulating the bacterial response to diverse antibiotics. The LuxS/AI-2 system is under the transcriptional control of the LsrR repressor. Despite this, the pathophysiological function of LsrR in pathogen-host interactions remains elusive. The results of the present study revealed that LsrR plays a crucial role in modulating various biological properties of APEC. Specifically, it inhibits sulfate transport, thereby reducing both the resistance of bacteria to oxidative stress and their survival within macrophages. In summary, LsrR is involved in the regulation of key processes during pathogen-host interactions. These findings provide promising prophylactic strategies for the prevention and control of APEC infections.