ZFIN ID: ZDB-PUB-100126-4
Burkholderia cenocepacia creates an intra-macrophage replication niche in zebrafish embryos, followed by bacterial dissemination and establishment of systemic infection
Vergunst, A.C., Meijer, A.H., Renshaw, S.A., and O'Callaghan, D.
Date: 2010
Source: Infection and Immunity   78(4): 1495-1508 (Journal)
Registered Authors: Meijer, Annemarie H., Renshaw, Steve A., Vergunst, Annette
Keywords: none
MeSH Terms:
  • Animals
  • Bacteremia/microbiology
  • Burkholderia Infections/immunology
  • Burkholderia Infections/veterinary*
  • Burkholderia cepacia complex/growth & development*
  • Cytoplasm/microbiology*
  • Disease Models, Animal
  • Female
  • Humans
  • Macrophages/microbiology*
  • Male
  • Microbial Viability
  • Survival Analysis
  • Virulence
  • Zebrafish/immunology
  • Zebrafish/microbiology*
PubMed: 20086083 Full text @ Infect. Immun.
Bacteria belonging to the 'Burkholderia cepacia complex' (Bcc) often cause fatal pulmonary infections in cystic fibrosis patients, yet little is know about the underlying molecular mechanisms. These Gram negative bacteria can adopt an intracellular life style, although their ability to replicate intracellularly has been difficult to demonstrate. Here we show that Bcc bacteria survive and multiply in macrophages of zebrafish embryos. Local dissemination by non-lytic release from infected cells was followed by bacteraemia and extracellular replication. Burkholderia cenocepacia isolates belonging to the epidemic ET12 lineage were highly virulent for the embryos, with intravenous injection of <10 bacteria of strain K56-2 killing embryos within three days. However, small but significant differences were evident between the clonal ET12 isolates K56-2, J2315 and BC7. In addition, the innate immune response in the young embryos was sufficiently developed to control infection with other less virulent Bcc strains, such as B. vietnamiensis FC441 and B. stabilis LMG14294. A K56-2 cepR quorum sensing regulator mutant was highly attenuated and greatly reduced in its ability to replicate and spread to neighbouring cells. Our data indicate that the zebrafish embryo is an excellent vertebrate model to dissect the molecular basis of intracellular replication and the early innate immune responses in this intricate host-pathogen interaction.