Glycosylation-dependent galectin–receptor interactions promote Chlamydia trachomatis infection

Abstract

() constitutes the most prevalent sexually transmitted bacterium worldwide. Chlamydial infections can lead to severe clinical sequelae including pelvic inflammatory disease, ectopic pregnancy, and tubal infertility. As an obligate intracellular pathogen, has evolved multiple strategies to promote adhesion and invasion of host cells, including those involving both bacterial and host glycans. Here, we show that galectin-1 (Gal1), an endogenous lectin widely expressed in female and male genital tracts, promotes infection. Through glycosylation-dependent mechanisms involving recognition of bacterial glycoproteins and -glycosylated host cell receptors, Gal1 enhanced attachment to cervical epithelial cells. Exposure to Gal1, mainly in its dimeric form, facilitated bacterial entry and increased the number of infected cells by favoring - and -host cell interactions. These effects were substantiated in vivo in mice lacking Gal1 or complex β1-6-branched-glycans. Thus, disrupting Gal1--glycan interactions may limit the severity of chlamydial infection by inhibiting bacterial invasion of host cells.

Pathogenic Puppetry: Manipulation of the Host Actin Cytoskeleton by Chlamydia trachomatis

“…The host component of this GAG-mediated bridge between EB and the host has remained elusive; however, recent work suggests an alternative, GAG-independent OmcB/MOMP attachment mechanism. Mounting evidence indicates that both proteins are post-translationally modified via glycosylation, as OmcB/MOMP recovered from EBs shows evidence of modification by N-linked high-mannose oligosaccharides [52][53][54]. Furthermore, both proteins exhibit reactivity to Erythrina crista-galli lectin, which binds to sites of N-acetyllactosamine glycosylation [54].…”

“…Mounting evidence indicates that both proteins are post-translationally modified via glycosylation, as OmcB/MOMP recovered from EBs shows evidence of modification by N-linked high-mannose oligosaccharides [52][53][54]. Furthermore, both proteins exhibit reactivity to Erythrina crista-galli lectin, which binds to sites of N-acetyllactosamine glycosylation [54]. It has been further shown that glycosylated OmcB and MOMP are recognized by the protein galectin-1 (Gal1), which is both secreted by the host and bound on the plasma membrane to surface receptors [54].…”

“…Furthermore, both proteins exhibit reactivity to Erythrina crista-galli lectin, which binds to sites of N-acetyllactosamine glycosylation [54]. It has been further shown that glycosylated OmcB and MOMP are recognized by the protein galectin-1 (Gal1), which is both secreted by the host and bound on the plasma membrane to surface receptors [54]. Given that galectin-1 can demonstrably bridge EBs to host Gal1 receptors [54], both its secreted and membrane-associated state could conceivably facilitate EB-host binding.…”

“…It has been further shown that glycosylated OmcB and MOMP are recognized by the protein galectin-1 (Gal1), which is both secreted by the host and bound on the plasma membrane to surface receptors [54]. Given that galectin-1 can demonstrably bridge EBs to host Gal1 receptors [54], both its secreted and membrane-associated state could conceivably facilitate EB-host binding. However, the latter state presents an intriguing avenue for the chlamydial induction of actin recruitment and invasion: in neurons, surface-associated Gal1 has been shown to initiate clathrin-independent endocytosis upon ligand binding, and Gal1 internalization is associated with F-actin polymerization during axonal growth [55].…”

“…In summary, ongoing study of actin modulation by Chlamydiae has revealed the multifaceted way in which these pathogens restructure the host actin cytoskeleton. During the two-stage attachment of chlamydial EBs to the host cell surface, the pathogen engages with a variety of host surface proteins-including galectin-1, FGFR, and PDGFRβ-that in turn facilitate the recruitment of signaling factors promoting actin polymerization at the attachment site [33,[52][53][54]63]. The subsequent delivery of chlamydial effectors by the pathogen's type III secretion system then induces actin-dependent invasion of the host cell.…”