부산대학교 도서관

All Chlamydia species are obligate intracellular bacteria that undergo a unique biphasic developmental cycle strictly in the lumen of a membrane bound compartment, the inclusion. Chlamydia specific Type III secreted effectors, known as inclusion membrane proteins (Inc), are embedded into the inclusion membrane. Progression through the developmental cycle, in particular early events of conversion from infectious (EB) to replicative (RB) bacteria, is important for intracellular replication, but poorly understood. Here, we identified the inclusion membrane protein IncS as a critical factor for Chlamydia development. We show that a C. trachomatis conditional mutant is impaired in transition from EB to RB in human cells, and C. muridarum mutant bacteria fail to develop in a mouse model of Chlamydia infection. Thus, IncS represents a promising target for therapeutic intervention of the leading cause of sexually transmitted infections of bacterial origin. Author summary: The identification and characterization of bacterial factors that are essential, or highly important, to the intracellular life style of obligate intracellular bacterial pathogens, for which limited genetic tools exist, present unique challenges. Here, we offer a blueprint to generate conditional mutants in Chlamydia trachomatis and Chlamydia muridarum, by combining existing genetic tools for Chlamydia, including an inducible promoter that is responsive in a murine model of Chlamydia infection. As a proof of concept, we present a conditional mutant in a Chlamydia inclusion membrane protein and show that is impaired in the early stages of the developmental cycle. Our study constitutes a major methodological advance to the study of Chlamydia and furthers our understanding of the bacterial factors contributing to progression through the developmental cycle. [ABSTRACT FROM AUTHOR]