Chlamydia spp. are obligate intracellular pathogens that replicate within a vacuole termed the inclusion. Chlamydiae extensively modify the inclusion membrane via the insertion of chlamydial inclusion membrane proteins (Incs) which decorate the cytosolic face of the inclusion. We have assessed the overall relatedness and phylogeny of Incs in order to identify potential evolutionary trends. Despite a high degree of conservation among Incs within C. trachomatis serovars, phylogenetic analysis showed that some Incs cluster according to clinical groupings suggesting that certain Incs may contribute to tissue tropism. Bioinformatic predictions identified Incs in five chlamydial species: 55 in C. trachomatis, 68 in C. felis, 92 in C. pneumoniae, 79 in C. caviae, and 54 in C. muridarum. Inc homologues were compared between chlamydial species and 23 core Incs were identified as shared among all species. Genomic expansion of Incs was identified in C. pneumoniae, C. caviae, and C. felis but not C. trachomatis or C. muridarum. 1. Introduction Chlamydiae are obligate intracellular pathogens that cause a variety of human and veterinary infections. Chlamydia trachomatis is the leading cause of preventable blindness worldwide and the most common bacterial sexually transmitted infection [1]. The species is comprised of 15 serovars that are associated with a wide spectrum of disease states including endemic trachoma (serotypes A to C), sexually transmitted infections (serotypes D to K), and a highly invasive granulomatous disease, lymphogranuloma venereum (LGV; serotypes L1 to L3) [1]. C. pneumoniae is a common cause of community acquired pneumonia and bronchitis [2] and has been linked to a spectrum of chronic diseases including atherosclerotic cardiovascular disease [3]. C. felis is a causative agent of feline chlamydiosis [4]. C. caviae and C. muridarum cause infections in guinea pigs and mice, respectively [5]. Despite the differences in host tropism and disease, all Chlamydia spp. share several unique properties. Chlamydiae undergo a biphasic developmental cycle consisting of metabolically inactive infectious elementary bodies (EBs) and metabolically active noninfectious, reticulate bodies (RBs). Within the host cell, chlamydiae reside in a parasitophorous vacuole called the inclusion whose interactions with the host cell are unlike any other intracellular pathogen in that it is nonfusogenic with the endocytic pathway but intercepts exocytic vesicular traffic from the Golgi apparatus [6–8]. The inclusion membrane is at the interface between the pathogen and the
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