摘要
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 proinflammatory factors IL-1βand TNF-α.Conclusion This study sheds light on the virulence factors of P.aeruginosa involved in meningitis.
基金
supported by National Natural Science Foundation of China,China(32170102)
Natural Science Foundation of Tianjin(21JCYBJC01420)
the Fundamental Research Funds for the Central Universities(63233050)。
