Preferential adherence of cable-piliated burkholderia cepacia to respiratory epithelia of CF knockout mice and human cystic fibrosis lung explants.
The Burkholderia cepacia complex consists of at least five well-documented bacterial genomovars, each of which has been isolated from the sputum of different patients with cystic fibrosis (CF). Although the world-wide prevalence of this opportunist pathogen in CF patients is low (1-3%), 'epidemic' clusters occur in geographically isolated regions. Prevalence in some of these clusters is as high as 30-40%. The majority of CF B. cepacia isolates belong to genomovar III, but the relationship between genomovar and virulence has not yet been defined. Because the initial stage of infection involves bacterial binding to host tissues, the present study investigated differences in the binding of representative isolates of all five genomovars to fixed nasal sections of UNC cftr (-/-) and (+/+) mice and to human lung explants, biopsy and autopsy tissue of CF and non-CF patients. Binding was highest for isolates of genomovar III, subgroup RAPD type 2, but only if the isolates expressed the cable pili phenotype. Antibodies to the 22-kDa adhesin of cable pili virtually abolished binding. Binding occurred only to cftr (-/-) nasal sections or to CF lung sections and was negligible in cftr (+/+) or human non-CF, histologically normal lung sections. Unlike normal epithelia, the hyperplastic epithelia of CF bronchioles were enriched in cytokeratin 13, a 55-kDa protein that has previously been shown to act as a receptor in vitro for cable-piliated B. cepacia. These findings may help to explain the high transmissibility ofCbl-positive, genomovar III strains of B. cepacia among CF patients.
Sajjan
Umadevi
U
Wu
Yijun
Y
Research Institute, Departments of Structural Biology and Biochemistry, *Developmental Biology and †Animal Laboratory Services, Hospital for Sick Children, Toronto, Ontario, Canada.
Kent
Geraldine
G
Research Institute, Departments of Structural Biology and Biochemistry, *Developmental Biology and †Animal Laboratory Services, Hospital for Sick Children, Toronto, Ontario, Canada.
Forstner
Janet
J
D018829:Adhesins, Bacterial / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry; D001422:Bacterial Adhesion / Q000235:genetics; D019121:Burkholderia Infections / Q000150:complications* / Q000453:epidemiology / Q000382:microbiology; D016956:Burkholderia cepacia / Q000235:genetics / Q000472:pathogenicity*; D002170:Canada / Q000453:epidemiology; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D017931:DNA Primers / Q000737:chemistry; D004269:DNA, Bacterial / Q000737:chemistry / Q000302:isolation & purification; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000382:microbiology; D006801:Humans; D007633:Keratins / Q000032:analysis; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000382:microbiology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014774:Virulence
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D017931:DNA Primers; D004269:DNA, Bacterial; D007633:Keratins