Deciphering Virulence Factors of Hyper-Virulent <i>Pseudomonas aeruginosa</i> Associated with Meningitis.

Li Ling XIE; Shuo LIU; Yu Fan WANG; Ming Chun LI; Zhen Hua HUANG; Yue MA; Qi Lin YU

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Deciphering Virulence Factors of Hyper-Virulent Pseudomonas aeruginosa Associated with Meningitis.

Author: Li Ling XIE ¹ ; Shuo LIU ¹ ; Yu Fan WANG ² ; Ming Chun LI ¹ ; Zhen Hua HUANG ³ ; Yue MA ³ ; Qi Lin YU ¹
Author Information

1. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, College of Life Sciences, Nankai University, Tianjin 300071, China.
2. Tianjin Third Central Hospital, Tianjin 300170, China.
3. Tianjin Huanhu Hospital, Tianjin 300350, China.
Publication Type:Journal Article
Keywords: Drug resistance; Genome sequencing; Meningitis; Pseudomonas aeruginosa; Virulence factor
MeSH: Pseudomonas aeruginosa/genetics*; Virulence Factors/metabolism*; Animals; Virulence; Mice; Pseudomonas Infections/microbiology*; Blood-Brain Barrier/microbiology*; Humans; Female
From: Biomedical and Environmental Sciences 2025;38(7):856-866
CountryChina
Language:English
Abstract: OBJECTIVE:Pseudomonas aeruginosa( P. aeruginosa) is a prevalent pathogenic bacterium involved in meningitis; however, the virulence factors contributing to this disease remain poorly understood.
METHODS:The virulence of the P. aeruginosa A584, isolated from meningitis samples, was evaluated by constructing in vitro blood-brain barrier and in vivo systemic infection models. qPCR, whole-genome sequencing, and drug efflux assays of A584 were performed to analyze the virulence factors.
RESULTS:Genomic sequencing showed that A584 formed a phylogenetic cluster with the reference strains NY7610, DDRC3, Pa58, and Pa124. Its genome includes abundant virulence factors, such as hemolysin, the Type IV secretion system, and pyoverdine. A584 is a multidrug-resistant strain, and its wide-spectrum resistance is associated with enhanced drug efflux. Moreover, this strain caused significantly more severe damage to the blood-brain barrier than the standard strain, PAO1. qPCR assays further revealed the downregulation of the blood-brain barrier-associated proteins Claudin-5 and Occludin by A584. During systemic infection, A584 exhibited a higher capacity of brain colonization than PAO1 (37.1 × 10 ⁶ CFU/g brain versus 2.5 × 10 ⁶ CFU/g brain), leading to higher levels of the pro-inflammatory factors IL-1β and TNF-α.
CONCLUSION:This study sheds light on the virulence factors of P. aeruginosa involved in meningitis.