Conservation of extrusion as an exit mechanism for Chlamydia.
Chlamydiae exit via membrane-encased extrusion or through lysis of the host cell. Extrusions are novel, pathogen-containing structures that confer infectious advantages to Chlamydia, and are hypothesized to promote cell-to-cell spread, dissemination to distant tissues and facilitate immune evasion. The extrusion phenomenon has been characterized for several Chlamydia trachomatis serovars, but a thorough investigation of extrusion for additional clinically relevant C. trachomatis strains and Chlamydia species has yet to be performed. The key parameters investigated in this study were: (i) the conservation of extrusion across the Chlamydia genus, (ii) the functional requirement for candidate Chlamydia genes in extrusion formation i.e. IncA and CT228 and (iii) extrusion-mediated uptake, and consequent survival of Chlamydia inside macrophages. Inclusion morphology was characterized by live fluorescence microscopy, using an inverted GFP strategy, at early and mid-stages of infection. Enriched extrusions were used to infect bone marrow-derived macrophages, and bacterial viability was measured following macrophage engulfment. Our results demonstrate that extrusion is highly conserved across chlamydiae, including ocular, STD and LGV biovars and divergent Chlamydia species. Consequently, this exit mechanism for Chlamydia may fulfill common advantages important for pathogenesis.
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA Program in Infectious Diseases, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Meghan
M
Zuck
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
Ashley
A
Sherrid
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
Robert
R
Suchland
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
Tisha
T
Ellis
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA khybiske@uw.edu.
Kevin
K
Hybiske
D005075:Biological Evolution; D002460:Cell Line; D022081:Cell Surface Extensions / Q000502:physiology*; D002689:Chlamydia / Q000502:physiology*; D002690:Chlamydia Infections / Q000382:microbiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
Chlamydia; dissemination; exit; extrusion; macrophage