A Type IV Secretion System Contributes to Intracellular Survival and Replication of Burkholderia cenocepacia

Abstract

Burkholderia cenocepacia is an important respiratory pathogen in persons with cystic fibrosis (CF). Recent studies indicate that B. cenocepacia survives within macrophages and airway epithelial cells in vitro by evading endosomelysosome fusion. We investigated the role of a plasmid-encoded type IV secretion system in the intracellular survival, replication, and processing of B. cenocepacia. Both a wild-type strain (K56-2) and its type IV secretion system mutant (designated LC101) entered and replicated in CF airway epithelial cells and monocyte-derived macrophages. However, significantly more intracellular K56-2 than LC101 bacteria were found in both cell types at 24 h postinfection. Colocalization of bacteria with markers of the classical endocytic pathway indicated that although both K56-2 and LC101 reside transiently in early endosomes, a greater proportion of the mutant bacteria are targeted to lysosomal degradation. In contrast, wild-type bacteria escape from the classical endocytic pathway and traffic to the endoplasmic reticulum, where they replicate. Our results show that the intracellular processing of B. cenocepacia is similar in both professional and nonprofessional phagocytes and that a functional plasmid-encoded type IV secretion system contributes to the survival and replication of B. cenocepacia in eukaryotic cells.

Phase variation has a role in Burkholderia ambifaria niche adaptation

“…Numerous factors involved in the virulence of Bcc strains have been identified, especially in B. cenocepacia Aubert et al, 2008;Sajjan et al, 2008). In our study, phenotypic and proteomic approaches reveal that transition from wild-type to variant affects the expression of several putative virulence factors, for instance, biofilm formation or protease activity.…”

Two type IV secretion systems with different functions in Burkholderia cenocepacia K56-2

“…We have reported previously that the plasmid-encoded Ptw T4SS plays a role in the intracellular survival of B. cenocepacia in both professional and non-professional phagocytes (Sajjan et al, 2008). A functional plasmidencoded T4SS contributes to the ability of B. cenocepacia to evade endocytic degradation, and to survive and replicate in both airway epithelial cells and monocyte-derived macrophages.…”

Dissecting novel virulent determinants in theBurkholderia cepaciacomplex

“…[1][2][3] Most Bcc species are also opportunistic mammalian pathogens, being particularly problematic for cystic fibrosis 4 (CF) patients and immune-compromised individuals. The two most clinically relevant species are B. cenocepacia and B. multivorans, accounting for .…”

“…7,8 Some Bcc members have gained attention as significant bacterial pathogens due to their high levels of intrinsic antibiotic resistance, 9,10 transmissibility in nosocomial settings, persistence in the presence of antimicrobials 11,12 and intracellular survival capabilities. 4,13 The Bcc are opportunistic pathogens and their arsenal of virulence factors includes proteases, lipases and other secreted exoproducts, including secretion system associated effectors. Understanding mechanisms of Bcc pathogenesis parallels and supports development of novel therapeutic approaches aimed at disarming the pathogens in the host.…”