title: Chlamydia trachomatis' struggle to keep its host alive.
abstract: Bacteria of the phylumChlamydiaeinfect a diverse range of eukaryotic host species, including vertebrate animals, invertebrates, and even protozoa. Characteristics shared by allChlamydiaeinclude their obligate intracellular lifestyle and a biphasic developmental cycle. The infectious form, the elementary body (EB), invades a host cell and differentiates into the replicative form, the reticulate body (RB), which proliferates within a membrane-bound compartment, the inclusion. After several rounds of division, RBs retro-differentiate into EBs that are then released to infect neighboring cells. The consequence of this obligatory transition between replicative and infectious forms inside cells is thatChlamydiaeabsolutely depend on the viability and functionality of their host cell throughout the entire infection cycle. We recently conducted a forward genetic screen inChlamydia trachomatis, a common sexually transmitted human pathogen, and identified a mutant that caused premature death in the majority of infected host cells. We employed emerging genetic tools inChlamydiato link this cytotoxicity to the loss of the protein CpoS (Chlamydiapromoter of survival) that normally localizes to the membrane of the pathogen-containing vacuole. CpoS-deficient bacteria also induced an exaggerated type-1 interferon response in infected cells, produced reduced numbers of infectious EBs in cell culture, and were cleared faster from the mouse genital tract in a transcervical infection modelin vivo. The analysis of this CpoS-deficient mutant yielded unique insights into the nature of cell-autonomous defense responses againstChlamydiaand highlighted the importance ofChlamydia-mediated control of host cell fate for the success of the pathogen.
authors.affiliation: INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France. ; Equipe 11 labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris 75006, France. ; Université Paris Descartes, Paris 75006, France. ; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif 94800, France.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Sixt
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Raphael H
authors.initials: RH
authors.lastname: Valdivia
authors.affiliation: INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France. ; Equipe 11 labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris 75006, France. ; Université Paris Descartes, Paris 75006, France. ; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif 94800, France. ; Pôle de Biologie, Hôpital Européen Georges-Pompidou, AP-HP, Paris 75015, France. ; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm 17176, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
keywords: Chlamydia; cell death; cell-autonomous defense; inclusion membrane protein; interferon response; vacuolar pathogen; virulence