title: Lack of effective anti-apoptotic activities restricts growth of Parachlamydiaceae in insect cells.
abstract: The fundamental role of programmed cell death in host defense is highlighted by the multitude of anti-apoptotic strategies evolved by various microbes, including the well-known obligate intracellular bacterial pathogens Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae. As inhibition of apoptosis is assumed to be essential for a successful infection of humans by these chlamydiae, we analyzed the anti-apoptotic capacity of close relatives that occur as symbionts of amoebae and might represent emerging pathogens. While Simkania negevensis was able to efficiently replicate within insect cells, which served as model for metazoan-derived host cells, the Parachlamydiaceae (Parachlamydia acanthamoebae and Protochlamydia amoebophila) displayed limited intracellular growth, yet these bacteria induced typical features of apoptotic cell death, including formation of apoptotic bodies, nuclear condensation, internucleosomal DNA fragmentation, and effector caspase activity. Induction of apoptosis was dependent on bacterial activity, but not bacterial de novo protein synthesis, and was detectable already at very early stages of infection. Experimental inhibition of host cell death greatly enhanced parachlamydial replication, suggesting that lack of potent anti-apoptotic activities in Parachlamydiaceae may represent an important factor compromising their ability to successfully infect non-protozoan hosts. These findings highlight the importance of the evolution of anti-apoptotic traits for the success of chlamydiae as pathogens of humans and animals.
authors.affiliation: Department of Microbial Ecology, University of Vienna, Vienna, Austria.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Sixt
authors.forename: Birgit
authors.initials: B
authors.lastname: Hiess
authors.forename: Lena
authors.initials: L
authors.lastname: König
authors.forename: Matthias
authors.initials: M
authors.lastname: Horn
mesh_terms: D000656:Amoeba / Q000187:drug effects / Q000382:microbiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002690:Chlamydia Infections / Q000382:microbiology; D002695:Chlamydiales / Q000187:drug effects / Q000254:growth & development*; D053938:DNA Fragmentation / Q000187:drug effects; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D013559:Symbiosis / Q000187:drug effects; D013997:Time Factors
chemical_list: D061945:Caspase Inhibitors; D011480:Protease Inhibitors; D020169:Caspases