Contribution of Burkholderia cenocepacia Flagella to Infectivity and Inflammation

Abstract

Burkholderia cenocepacia is an opportunistic pathogen that can cause severe lung infections in cystic fibrosis patients. To understand the contribution of B. cenocepacia flagella to infection, a strain mutated in the major flagellin subunit, fliCII, was constructed in B. cenocepacia K56-2 and tested in a murine agar bead model of lung infection. C57/BL6 mice infected with ϳ10 8 wild-type K56-2 bacteria exhibited 40% mortality after 3 days, whereas no mortality was noted in mice infected with the fliCII mutant. Among the mice surviving the infection with either strain, there was no significant difference in the bacterial loads in the lungs and spleen, bacteremia, weight loss, or infiltration of immune effector cells at 3 days postinfection. Similar results were observed at 24 h, prior to expression of the lethality phenotype. KC, a murine interleukin-8 (IL-8) homolog, was elevated in both the bronchoalveolar lavage fluid and serum of mice infected with the wild type compared to the fliCII mutant at 24 h, suggesting that flagella stimulated host cells. To demonstrate that flagella contributed to these responses, the interaction between B. cenocepacia and Toll-like receptor 5 (TLR5) was investigated. Infection of HEK293 cells with heat-killed wild-type K56-2, but not infection with the fliCII mutant, resulted in both NF-B activation and IL-8 secretion that was dependent upon expression of TLR5. Together, these results demonstrate that B. cenocepacia flagella contribute to virulence in an in vivo infection model, and that induction of host immune responses through interaction with TLR5 may contribute to its overall pathogenic potential.

Growth on mannitol-rich media elicits a genome-wide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner

“…The flagella of B. cenocepacia have been shown to be required for full virulence within a murine infection model (Urban et al, 2004) and for efficient invasion of respiratory epithelial cells in vitro (Tomich et al, 2002). Given the enhanced motility of B. multivorans observed in MYEM, we examined whether growth in mannitol influenced the ability to invade A549 alveolar epithelial cells.…”

Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped for versatility

“…Although the genetic factors required for animal and human pathogenicity by Burkholderia are largely unknown, multiple traits have been experimentally implicated in the virulence of B. pseudomallei (20) and the Bcc (12) ( Table 6, which is published as supporting information on the PNAS web site). Resistance to cationic antimicrobial agents such as polymixin B, presence of a flagellum (49), and iron acquisition by siderophores (50) (pyoverdin, pyochelin biosynthesis, chromosome 1) are virulence traits but also important in their soil habitat. Also, several genes are present that may mediate resistance to reactive oxygen species and enable LB400 to survive within intracellular environments.…”

Comparative analysis of proteins in the culture supernatants of human intestinal epithelial cells infected with the wild-type and rtxE mutant of Vibrio vulnificus

“…Interestingly, the flagellins of V. vulni ficus, known as TLR5 ligands, were present in abundance in the co-culture supernatants. Recently, uropathogenic E. coli has been shown to activate IL-8 production via P-fimbriae, and the flagellins of different enteropathogenic bacteria and V. vulnificus flagellin have been determined to activate IL-8 production via TLR5 (37)(38)(39).…”