The PapG tip adhesin of P fimbriae protects Escherichia coli from neutrophil bactericidal activity.
Compared with Escherichia coli ORN103, a nonfimbriated K-12 strain, P-fimbriated E. coli ORN103/pPAP5 was found to interact poorly with human neutrophils and resist their bactericidal activity in vitro. PapG, the Gal alpha(1-->4)Gal binding moiety located at the distal end of the P fimbrial filament, appeared to be responsible for this effect because an isogenic PapG- mutant, E. coli ORN103/pPAP24, exhibited binding interactions with neutrophils that were similar to nonfimbriated E. coli ORN103. Although no direct evidence is available, the poor adherence mediated by PapG could be related to its electrostatic properties because the isolated PapG protein had a pI of 5.2, which indicated that in the physiological pH range it possessed a net negative charge. Antibodies against PapG overcame the protective effect of PapG and markedly enhanced the interactions of P-fimbriated E. coli with neutrophils resulting in bacterial killing. When a P-fimbriated clinical E. coli strain or its isogenic PapG- derivative was injected into the peritoneal cavities of mice, a similar number of neutrophils was recruited to the site of injection. After 2 h, the number of P-fimbriated E. coli organisms that survived the neutrophil influx in the mouse peritoneum was approximately four times more than the number of surviving PapG- bacteria. This result demonstrates that the PapG protein, which is strategically located at the distal region of the P-fibrillum structure, protects E. coli from the bactericidal action of neutrophils.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
R
R
Tewari
T
T
Ikeda
R
R
Malaviya
J I
JI
MacGregor
J R
JR
Little
S J
SJ
Hultgren
S N
SN
Abraham
D000818:Animals; D002240:Carbohydrate Sequence; D002448:Cell Adhesion; D002465:Cell Movement; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000648:ultrastructure; D004927:Escherichia coli Infections / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D010538:Peritonitis / Q000382:microbiology; D014774:Virulence / Q000276:immunology