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J Infect Dis. 2014 Apr 1;209(7):1066-76. doi: 10.1093/infdis/jit619. Epub 2013 Nov 20.

Complement protective epitopes and CD55-microtubule complexes facilitate the invasion and intracellular persistence of uropathogenic Escherichia coli.

Author information

1
Department of Microbiology and Immunology.

Abstract

BACKGROUND:

 Escherichia coli-bearing Dr-adhesins (Dr+ E. coli) cause chronic pyelonephritis in pregnant women and animal models. This chronic renal infection correlates with the capacity of bacteria to invade epithelial cells expressing CD55. The mechanism of infection remains unknown.

METHODS:

 CD55 amino acids in the vicinity of binding pocket-Ser155 for Dr-adhesin were mutated to alanine and subjected to temporal gentamicin-invasion/gentamicin-survival assay in Chinese hamster ovary cells. CD55/microtubule (MT) responses were studied using confocal/electron microscopy, and 3-dimensional structure analysis.

RESULTS:

 Mutant analysis revealed that complement-protective CD55-Ser165 and CD55-Phe154 epitopes control E. coli invasion by coregulating CD55-MT complex expression. Single-point CD55 mutations changed E. coli to either a minimally invasive (Ser165Ala) or a hypervirulent pathogen (Phe154Ala). Thus, single amino acid modifications with no impact on CD55 structure and bacterial attachment can have a profound impact on E. coli virulence. While CD55-Ser165Ala decreased E. coli invasion and led to dormant intracellular persistence, intracellular E. coli in CD55-Phe154Ala developed elongated forms (multiplying within vacuoles), upregulated CD55-MT complexes, acquired CD55 coat, and escaped phagolysosomal fusion.

CONCLUSIONS:

 E. coli target complement-protective CD55 epitopes for invasion and exploit CD55-MT complexes to escape phagolysosomal fusion, leading to a nondestructive parasitism that allows bacteria to persist intracellularly.

KEYWORDS:

CD55; Dr+ E. coli; intracellular persistence; invasion; microtubules

PMID:
24259524
PMCID:
PMC3975163
DOI:
10.1093/infdis/jit619
[Indexed for MEDLINE]
Free PMC Article

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