Chlamydia attachment to mammalian cells requires protein disulfide isomerase

Abstract

SummaryFor Chlamydia, an intracellular pathogen of humans, host cell invasion is obligatory for survival, growth and pathogenesis. At the molecular level, little is known about the binding and entry of Chlamydia into the mammalian host cell. Chlamydia are genetically intractable therefore experimental approaches targeting the host are often necessary. CHO6 is a mutagenized cell line resistant to attachment and infection by Chlamydia. In this study, CHO6 was shown using proteomic methods to have a defect in processing of the leader sequence for protein disulfide isomerase (PDI). Complementation by expression of full-length PDI restored C. trachomatis binding and infectivity in the CHO6 mutant cell line. The cell line was also resistant to diphtheria toxin and required complemented cell-surface PDI for toxin entry. These data demonstrate that native PDI at the cell surface is required for effective chlamydial attachment and infectivity.

Identification and enzymatic activities of four protein disulfide isomerase (PDI) isoforms of Leishmania amazonensis

“…In parasites such as Neospora caninum and Toxoplasma gondii, PDI was reported as playing a role in the parasite-host cell interaction (Liao et al 2006;Robinson and Roy 2006). Moreover, it has recently been shown that native PDI on the cell surface is required for the effective attachment of Chlamydia, an obligate intracellular bacterial pathogen of eukaryotic cells (Conant and Stephens 2007). Likewise, a 52-kDa PDI of N. caninum techyzoites is involved in the adhesion of parasites to host cells (Naguleswaran et al 2005).…”

Attachment ofChlamydia trachomatisL2 to host cells requires sulfation

“…Using chemical mutagenesis, Carabeo et al (8) isolated a CHO cell clone resistant to Chlamydia, and Fudyk et al (9) found 12 CHO clones that are resistant to Chlamydia, but had difficulty identifying the mutations that impart resistance. Only one of the 12 clones initially identified was subsequently characterized as carrying a mutation in protein disulfide isomerase (10). Chemical mutagenesis screens suffer from the fact that a great many genes will be altered because of the dose of mutagen required to obtain a pool of mutants that can be screened.…”

Roles of Cellular Redox Factors in Pathogen and Toxin Entry in the Endocytic Pathways

“…During EB attachment, exposure of HEC-1B cells to three different inhibitors of PDI reductive activity (DTNB, bacitracin, and anti-PDI antibodies) resulted in reduced chlamydial infection. Subsequently, a proteomic study of CHO6 cell line [121], a mutagenized cell line resistant to attachment and infection by Chlamydia, showed that CHO6 has a defect in processing of the leader sequence of PDI, which results in altered cellular distribution of PDI. PDI is abundantly localized in the ER, and surface localization is predominantly sequestered to large patches compared to the punctate pattern in the wild type CHOK1 cells.…”