A decade of Burkholderia cenocepacia virulence determinant research

Abstract

The Burkholderia cepacia complex (Bcc) is a group of genetically related environmental bacteria that can cause chronic opportunistic infections in patients with cystic fibrosis (CF) and other underlying diseases. These infections are difficult to treat due to the inherent resistance of the bacteria to antibiotics. Bacteria can spread between CF patients through social contact and sometimes cause cepacia syndrome, a fatal pneumonia accompanied by septicemia. Burkholderia cenocepacia has been the focus of attention because initially it was the most common Bcc species isolated from patients with CF in North America and Europe. Today, B. cenocepacia, along with Burkholderia multivorans, is the most prevalent Bcc species in patients with CF. Given the progress that has been made in our understanding of B. cenocepacia over the past decade, we thought that it was an appropriate time to review our knowledge of the pathogenesis of B. cenocepacia, paying particular attention to the characterization of virulence determinants and the new tools that have been developed to study them. A common theme emerging from these studies is that B. cenocepacia establishes chronic infections in immunocompromised patients, which depend more on determinants mediating host niche adaptation than those involved directly in host cells and tissue damage.

FIG. 1.

Representation of the localization and known functions of B. cenocepacia virulence determinants. All of the established and proposed virulence determinants are discussed in the appropriate subsections of this review. BDSF denotes cis-2-dodecenoic acid, diffusible, nonhomoserine lactone signal molecule. Virulence determinants with proposed or unknown functions are denoted with question marks. (Inset A) Bacteria fixed in the presence of alcian blue and stained with uranyl acetate and lead citrate to visualize the extracellular matrix produced by bacterial cells from the virulent rough colony morphology phenotype described by Bernier et al. (14). The exact composition of this extracellular matrix is unknown but is proposed to consist of exopolysaccharide and possibly lipopolysaccharide and proteins (14). (Inset B) Bacterial cells negatively stained with uranyl acetate to visualize flagella. Bars, 0.5 μm. (Electron micrographs courtesy of Maria Soledad Saldías, reproduced with permission.)