High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection.
Fan YangYuchen ZhouPeishan ChenZeqiong CaiZhuo YueYongxin JinZhihui ChengWeihui WuLiang YangUn-Hwan HaFang BaiPublished in: Infection and immunity (2022)
Bloodstream infections (BSIs) caused by Pseudomonas aeruginosa are associated with a high mortality rate in the clinic. However, the fitness mechanisms responsible for the evolution of virulence factors that facilitate the dissemination of P. aeruginosa to the bloodstream are poorly understood. In this study, a transcriptomic analysis of the BSI-associated P. aeruginosa clinical isolates showed a high-level expression of cell-surface signaling (CSS) system Hxu. Whole-genome sequencing and comparative genomics of these isolates showed that a mutation in rnfE gene was responsible for the elevated expression of the Hxu-CSS pathway. Most importantly, deletion of the hxuIRA gene cluster in a laboratory strain PAO1 reduced its BSI capability while overexpression of the HxuIRA pathway promoted BSI in a murine sepsis model. We further demonstrated that multiple components in the blood plasma, including heme, hemoglobin, the heme-scavenging proteins haptoglobin, and hemopexin, as well as the iron-delivery protein transferrin, could activate the Hxu system. Together, these studies suggested that the Hxu-CSS system was an important signal transduction pathway contributing to the adaptive pathogenesis of P. aeruginosa in BSI.
Keyphrases
- pseudomonas aeruginosa
- cell surface
- poor prognosis
- cystic fibrosis
- biofilm formation
- single cell
- long non coding rna
- genome wide
- acute kidney injury
- intensive care unit
- physical activity
- primary care
- risk factors
- body composition
- cardiovascular disease
- transcription factor
- gene expression
- coronary artery disease
- genetic diversity
- amino acid
- small molecule
- protein protein