Infectivity ofChlamydia trachomatisSerovar LGV but Not E Is Dependent on Host Cell Heparan Sulfate

Abstract

The ability of heparan sulfate, heparin, and other glycosaminoglycans to inhibit the infectivity of Chlamydia trachomatis serovars E and LGV was examined using a simple competitive inhibition assay with three cell types from the human female reproductive tract, including primary human endosalpingeal cells. With the majority of the glycosaminoglycans tested, LGV was more significantly inhibited than serovar E. We have compared chlamydial infectivity between a wild-type Chinese hamster ovary cell line and two glycosaminoglycan-deficient cell lines.LGV was shown to be unable to infect heparan sulfate-deficient and GAG-deficient Chinese hamster ovary cell lines, whereas the E serovar infected these cells as efficiently as the control (nondeficient) cells. These two sets of experiments confirmed that serovar LGV is more dependent on a heparan sulfate-related mechanism of infectivity than is serovar E. This is further supported by the fact that attempts to purify a heparan sulfate-like molecule from either serovar cultured in glycosaminoglycan-deficient cell lines were nonproductive. Previous reports have suggested that chlamydia are able to produce a heparan sulfate-like molecule that is important for attachment and infectivity. We have attempted to detect possible binding of a specific heparan sulfate antibody to C. trachomatis by flow cytometry. Results showed no binding of the heparan sulfate antibody to C. trachomatis serovar LGV or E. Our results strongly indicate that chlamydiae do not produce a heparan sulfate-like molecule but rather use host cell heparan sulfate in order to infect cells.

Chlamydophila pneumoniae attachment and infection in low proteoglycan expressing human lymphoid Jurkat cells

“…Our study confirmed that following bacterial attachment, typical inclusions formed that were permissive to bacterial growth, resulting in increased infectious progenies in [17][18][19][20][21][22]. Heparin, which forms the majority of GAGs, also plays a critical role in host cells as a receptor for the attachment of the other pathogens such as Bordetella pertussis [35], Hemophilus influenzae [36] or Neisseria gonorrhoeae [37].…”

“…Heparin independent attachment and host invasion has also been described for the C. trachomatis LGV invasive serotype causing a systemic disease, but not for any other serotypes [17][18][19][20][21][22]. This suggests that a heparin-independent attachment mechanism is useful for a pathogen to effectively spread from local lesions, such as the genital tract in this case, to other distinct lymphoid tissue, as observed in pelvic inflammatory disease [42].…”

“…Host cell attachment is critical in the pathogenic cycle of Chlamydia or Chlamydophila species and the underlying mechanisms involved have been extensively studied over many years using epithelial cells, such as HeLa cells, HEp-2 cells, or McCoy cells [17][18][19][20]. Data from these experiments suggest that heparin, which is the most common GAG, covalently attaches to the core proteins of PG expressed on the host cells and critically functions as a receptor against chlamydial adhesions, such as the outer membrane protein, OmcB [21] or stress protein, GroEL1 [22].…”

Attachment ofChlamydia trachomatisL2 to host cells requires sulfation

“…CHO cells deficient in enzymes in the heparan sulfate pathway (PgsA-745, PgsD-677, and CHO-761) (4,36) show decreased infectivity with Chlamydia compared with the parental CHO-K1 line. No reconstitution of chemically mutagenized Chlamydia-resistant CHO cell lines has been reported, presumably because such lines are heavily mutagenized to begin with, complicating identification of the mutations responsible for resistance.…”

Enhanced bacterial virulence through exploitation of host glycosaminoglycans

“…In spite of these observations, GAG synthesis by Chlamydia remains controversial, as Taraktchoglou et al (2001) failed to detect chlamydial heparan sulphate-like compounds on some serovars. Moreover, analysis of the completed genomes of C. trachomatis and Chlamydia pneumoniae provided no evidence for chlamydial GAG biosynthesis-related genes (Hackstadt, 1999).…”