High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection

Yang，Fan1; Zhou，Yuchen1; Chen，Peishan2; Cai，Zeqiong1; Yue，Zhuo1; Jin，Yongxin1; Cheng，Zhihui1; Wu，Weihui1; Yang，Liang3; Ha，Un Hwan4; Bai，Fang1

2022-10-01

10.1128/iai.00329-22

INFECTION AND IMMUNITY   Impact Factor & Quartile

0019-9567

1098-5522

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 hemescavenging 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.

bloodstream infections cell-surface signaling ECF sigma factor Hxu Pseudomonas aeruginosa Rnf

SCI

English

Others

WOS:000861848900001

IMMUNOLOGY

2-s2.0-85140415381

Scopus

1.State Key Laboratory of Medicinal Chemical Biology,Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education,College of Life Sciences,Nankai University,Tianjin,China
2.Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair,Institute of Acute Abdominal Diseases,Tianjin Nankai Hospital,Tianjin,China
3.School of Medicine,Southern University of Science and Technology (SUSTec),Shenzhen,China
4.Department of Biotechnology and Bioinformatics,Korea University,Sejong,South Korea

Yang，Fan,Zhou，Yuchen,Chen，Peishan,et al. High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection[J]. INFECTION AND IMMUNITY,2022,90(10).

Yang，Fan.,Zhou，Yuchen.,Chen，Peishan.,Cai，Zeqiong.,Yue，Zhuo.,...&Bai，Fang.(2022).High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection.INFECTION AND IMMUNITY,90(10).

Yang，Fan,et al."High-Level Expression of Cell-Surface Signaling System Hxu Enhances Pseudomonas aeruginosa Bloodstream Infection".INFECTION AND IMMUNITY 90.10(2022).