Molecular characterization of arginine deiminase pathway in Laribacter hongkongensis and unique regulation of arginine catabolism and anabolism by multiple environmental stresses

Abstract

The betaproteobacterium Laribacter hongkongensis is associated with invasive bacteremic infections and gastroenteritis. Its genome contains two adjacent arc gene cassettes (arc1 and arc2) under independent transcriptional control, which are essential for acid resistance. Laribacter hongkongensis also encodes duplicate copies of the argA and argB genes from the arginine biosynthesis pathway. We show that arginine enhances the transcription of arcA2 but suppresses arcA1 expression. We demonstrate that ArgR acts as a transcriptional regulator of the two arc operons through binding to ARG operator sites (ARG boxes). Upon temperature shift from 20°C to 37°C, arcA1 transcription is upregulated while arcA2, argA2, argB2 and argG are downregulated. The transcription of arcA1 and arcA2 are augmented under anaerobic and acidic conditions. The transcription levels of argA1, argA2, argB1, argB2 and argG are significantly increased under anaerobic and acidic conditions but are repressed by the addition of arginine. Deletion of argR significantly decreases bacterial survival in macrophages, while expression of both arc operons, argR and all five of the anabolic arg genes increases 8 h post-infection. Our results show that arginine catabolism in L. hongkongensis is finely regulated by controlling the transcription of two arc operons, whereas arginine anabolism is controlled by two copies of argA and argB.