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Article | Open Access

Emergence of hypervirulent Pseudomonas aeruginosa pathotypically armed with co-expressed T3SS effectors ExoS and ExoU

Yuqin Song1,#, Yongqi Mu1,7,#, Nai-Kei Wong2,#, Zhuo Yue3,#, Juan Li4,#, Min Yuan4, Xiong Zhu5, Jinshu Hu6, Gang Zhang1, Dawei Wei1,7, Chao Wang1, Weihui Wu3, Fang Bai3( ), Jie Feng1( )
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Clinical Pharmacology Section, Department of Pharmacology, Shantou University Medical College, Guangdong, China
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
State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Department of Clinical Laboratory, People’s Hospital of Sanya, Hainan, China
Cangzhou Central Hospital, Hebei, China
College of Life Science, University of Chinese Academy of Sciences, Beijing, China

# These authors contributed equally to this work

Show Author Information

Highlights

● CAI-associated exoS+/exoU+ Pseudomonas aeruginosa strains have emerged as a new subset of hypervirulent P. aeruginosa.

● The co-expression and co-secretion of T3SS effectors ExoS and ExoU enhanced exoS+/exoU+ strains’ potentials for cytotoxicity in vitro and pathogenicity in vivo.

● ExoU acquisition of exoS+ P. aeruginosa is likely mediated by HGT of pathogenicity island PAPI-2.

● ExoS+/exoU+ P. aeruginosa strains had widely distributed across the globe, highlighting an urgent need for surveillance against these high-risk strains.

Graphical Abstract

Abstract

Pseudomonas aeruginosa is a significant pathogen mainly causing healthcare-associated infections (HAIs). Newly emerging high-risk clones of P. aeruginosa with elevated virulence profiles furtherly cause severe community-acquired infections (CAIs). Usually, it is not common for P. aeruginosa to co-carry exoU and exoS genes, encoding two type Ⅲ secretion system (T3SS) effectors. The pathogenicity mechanism of exoS+/exoU+ strains of P. aeruginosa remains unclear. Here, we provide detailed evidence for a subset of hypervirulent P. aeruginosa strains, which abundantly co-express and secrete the T3SS effectors ExoS and ExoU. The exoS+/exoU+ P. aeruginosa strains were available to cause both HAIs and CAIs. The CAI-associated strains could elicit severe inflammation and hemorrhage, leading to higher death rates in a murine acute pneumonia model, and had great virulence potential in establishing chronic infections, demonstrating hypervirulence when compared to PAO1 (exoS+/exoU) and PA14 (exoS-/exoU+). Both ExoS and ExoU were co-expressed and co-secreted in abundance in exoS+/exoU+ strains. Their abundant protein secretion could boost exoS+/exoU+ strains’ potentials for cytotoxicity in vitro and pathogenicity in vivo. Genomic evidence indicates that exoU acquisition is likely mediated by horizontal gene transfer (HGT) of the pathogenicity island PAPI-2, while deletion of exoU was sufficient to mitigate virulence in the exoS+/exoU+ strains. Furthermore, bioinformatics analysis showed that such exoS+/exoU+ P. aeruginosa strains turned out to be widely distributed across the globe. Overall, the research provide detailed evidence for the high virulence and epidemicity of exoS+/exoU+ strains of P. aeruginosa, highlighting an urgent need for surveillance against these high-risk hypervirulent strains.

Keywords

Hypervirulent Pseudomonas aeruginosacommunity-acquired infectiontype Ⅲ secretion system (T3SS)co-expressed ExoS and ExoUpathogen surveillance

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hLife
Volume 1 Issue 1,
November 2023
Pages 44-56
DOI: 10.1016/j.hlife.2023.02.001
Cite this article:
Song Y, Mu Y, Wong N-K, et al. Emergence of hypervirulent Pseudomonas aeruginosa pathotypically armed with co-expressed T3SS effectors ExoS and ExoU. hLife, 2023, 1(1): 44-56. https://doi.org/10.1016/j.hlife.2023.02.001

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Received: 31 December 2022
Revised: 30 January 2023
Accepted: 08 February 2023
Published: 28 March 2023
© 2023 The Author(s).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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