Tentative identification of glycerol dehydrogenase as Escherichia coli K1 virulence factor cglD and its involvement in the pathogenesis of experimental neonatal meningitis.
Escherichia coli (E. coli) is the most common gram-negative organism causing meningitis during the neonatal period. The mechanism involved in the pathogenesis of E. coli meningitis remains unclear. We previously identified a pathogenicity island GimA (genetic island of meningitic E. coli containing ibeA) from the genomic DNA library of E. coli K1, which may contribute to the E. coli invasion of the blood-brain barrier (BBB). CglD is one of the genes in GimA, and its function remains unknown. In order to characterize the role of cglD in the E. coli meningitis, an isogenic in-frame cglD deletion mutant of E. coli K1 was generated. The results showed that the median lethal dose of the cglD deletion mutant strain was significant higher than that of parent E. coli K1 strain, and the cglD deletion in E. coli K1 prolonged survival of the neonatal rats in experimental meningitis. However, deletion of cglD has no effect on the penetration of E. coli K1 through BBB in vitro and in vivo. Furthermore, our results showed that deletion of cglD in E. coli K1 attenuated cerebrospinal fluid changes, meningeal thickening, and neutrophil infiltration in the cerebral cortex in the neonatal rats with experimental meningitis. Additional results showed that the role of CglD in neonatal meningitis may be associated with its activity of glycerol dehydrogenase. Taken together, our study suggested that CglD is a virulence factor of E. coli K1 contributed to the development of neonatal meningitis.
Zhang
Ke
K
Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, People's Republic of China.
Zhao
Wei-Dong
WD
Li
Qiang
Q
Fang
Wen-Gang
WG
Zhu
Li
L
Shang
De-Shu
DS
Chen
Yu-Hua
YH
D000818:Animals; D001422:Bacterial Adhesion; D001812:Blood-Brain Barrier / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007928:Lethal Dose 50; D020814:Meningitis, Escherichia coli / Q000382:microbiology*; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D017384:Sequence Deletion; D013401:Sugar Alcohol Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D029968:Escherichia coli Proteins; D037521:Virulence Factors; D013401:Sugar Alcohol Dehydrogenases; C020672:glycerol dehydrogenase