Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes

Abstract

Chlamydia trachomatis is an obligate intracellular human bacterial pathogen that infects epithelial cells of the eye and genital tract. Infection can result in trachoma, the leading cause of preventable blindness worldwide, and sexually transmitted diseases. A common feature of infection is a chronic damaging inflammatory response for which the molecular pathogenesis is not understood. It has been proposed that chlamydiae have a cytotoxic activity that contributes to this pathology, but a toxin has not been identified. The C. trachomatis genome contains genes that encode proteins with significant homology to large clostridial cytotoxins. Here we show that C. trachomatis makes a replication-independent cytotoxic activity that produces morphological and cytoskeletal changes in epithelial cells that are indistinguishable from those mediated by clostridial toxin B. A mouse chlamydial strain that encodes a full-length cytotoxin caused pronounced cytotoxicity, as did a human strain that has a shorter ORF with homology to only the enzymatically active site of clostridial toxin B. Cytotoxin gene transcripts were detected in chlamydiae-infected cells, and a protein with the expected molecular mass was present in lysates of infected epithelial cells. The protein was present transiently in infected cells during the period of cytotoxicity. Together, these data provide compelling evidence for a chlamydial cytotoxin for epithelial cells and imply that the cytotoxin is present in the elementary body and delivered to host cells very early during infection. We hypothesize that the cytotoxin is a virulence factor that contributes to the pathogenesis of C. trachomatis diseases.

Chlamydial IFN-γ immune evasion is linked to host infection tropism

“…7. A major difference between MoPn and C. trachomatis strains maps to a cytotoxin loci located in the plasticity zone (12,25). MoPn encodes three copies of a large (Ϸ350 kDa) protein, each containing domains with homology to the UDP-glycosyltransferase portion of the large clostridial toxin (LCT) and the type III secreted Yersinia pestis cysteine protease YopT (12,25).…”

Chlamydia trachomatis: Genome sequence analysis of lymphogranuloma venereum isolates

“…The variation in size of the C. trachomatis PZ is largely due to differential deletion of the cytotoxin gene(s), which have been almost entirely deleted from strain L2, leaving two gene remnants CTL0420 and CTL0421 (Belland et al 2001;Carlson et al 2004) (Fig. 3).…”

Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis

“…Upon entering host cells, the parasite starts a biphasic developmental cycle from the infectious form, called an elementary body, to a non-infectious, vegetative growth form, called a reticulate body, and then eventually back to the replication-incompetent infectious form (2). After the transition back to the infectious form, the host cell dies and releases its infectious load (3). To accommodate its life cycle, Chlamydia may inhibit apoptosis during the early stages of infection (4,5) and promote apoptosis at later stages (6,7).…”