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 di fferent patients with cystic fibrosis (CF), Although the world-wide prevale nce of this opportunist pathogen in CF patients is low (1-3%), 'epidemic' c lusters occur in geographically isolated regions. Prevalence in some of the se clusters is as high as 30-40%, The majority of CF B. cepacia isolates be long 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 differenc es in the binding of representative isolates of all five genomovars to fixe d nasal sections of UNC cftr (-/-) and (+/+) mice and to human lung explant s, 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 isola tes expressed the cable pill phenotype, Antibodies to the 22-kDa adhesin of cable pill 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 i n vitro for cable-piliated B, cepacia, These findings may help to explain t he high transmissibility of Cbl-positive, genomovar III strains of B, cepac ia among CF patients.