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

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.