Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture

Yabushita, Hiromitsu; Noguchi, Yasuyuki; Habuchi, Hiroko; Ashikari, Satoko; Nakabe, Ken; Fujita, Masaru; Noguchi, Masayoshi; Esko, Jeffrey D.; Kimata, Koji

doi:10.1093/glycob/12.5.345

Cited by 21 publications

(23 citation statements)

References 30 publications

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“…With deference to some previous interpretations (20,21,23,24), minor reductions in chlamydial attachment or infectivity for CHO-677, CHO-745, or CHO-761 mutant cells are insufficient to warrant a conclusion that host cell heparan sulfate serves as a receptor for chlamydiae. These reproducible reductions in infectivity appear to be an epiphenomenon of chemical mutagenesis unrelated to the mutant cell's lack of glycosaminoglycan production.…”

Section: Discussionmentioning

confidence: 78%

“…Comprehensive characterization of CHO-761 has shown that it is as deficient in heparan and chondroitin sulfate biosynthesis as is CHO-745 (1, 7). It has previously been shown that sulfated oligosaccharides are required for competitive inhibition of chlamydial infectivity (5); however, consistent with the lack of a functional role for host cell glycosaminoglycans, Yabushita et al (24) found no inhibition of chlamydial infectivity for a mutant cell line deficient in sulfated glycosaminoglycans.…”

Section: Discussionmentioning

confidence: 90%

“…Each report to date has shown that CHO-677, CHO-745, and CHO-761 cells are less sensitive than the parental CHO-K1 to infection by C. trachomatis and C. pneumoniae by factors ranging from two-to ninefold. Several investigators have proposed that host cell surface heparan sulfate is either essential for chlamydial infection (23) or is the host cell receptor for chlamydia (20,21,24).…”

Section: Discussionmentioning

confidence: 99%

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Interaction of Chlamydia trachomatis with Mammalian Cells Is Independent of Host Cell Surface Heparan Sulfate Glycosaminoglycans

2006

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The hypothesis that host cell surface heparan sulfate is required to promote chlamydial infection was tested using a cell line (CHO-18.4) containing a single retroviral insertion and the concomitant loss of heparan sulfate biosynthesis. Tests of chlamydial infectivity of heparan sulfate-deficient CHO-18.4 cells and parental cells, CHO-22, demonstrated that both were equally sensitive to infection by Chlamydia trachomatis serovars L2 and D. These data do not support the hypothesis and demonstrate that host cell surface heparan sulfate does not serve an essential functional role in chlamydial infectivity.Investigations of chlamydial infection of mammalian host cells have produced several published studies that have utilized Chinese hamster ovary (CHO) cell mutants deficient in the synthesis of heparan sulfate and/or chondroitin sulfate. CHO-677 is deficient in the synthesis of heparan sulfate because it lacks both N-acetylglucosaminyltransferase and glucuronosyltransferase activities necessary for polymerization of heparan sulfate chains but produces increased amounts of chondroitin sulfate (16). CHO-745 is deficient in the synthesis of both heparan sulfate and chondroitin sulfate because it lacks xylosyltransferase activity required for the initiating step in glycosaminoglycan synthesis (6). CHO-761 lacks galactosyltransferase I for the second step in glycosaminoglycan synthesis and like CHO-745 does not produce heparan sulfate and chondroitin sulfate (7).In the report by Zhang and Stephens (26) that investigated the functional role of heparan sulfate and chlamydial infectivity in vitro, it was proposed that heparan sulfate-like molecules bound to chlamydial surfaces and bridged binding to host cells, resulting in infection independent of host cell surface heparan sulfate. Consistent with this hypothesis, only small reductions (ca. twofold) in susceptibility to chlamydial infection were observed for heparan sulfate-deficient CHO-761 cells (26). Larger reductions were observed for CHO-677 and CHO-745 cells (four-to eightfold); nevertheless, like the parental cell line CHO-K1, each cell line can readily be Ͼ90% infected using static inoculation (18). It was concluded that the reductions in infectivity for these CHO cell mutants were less than would be expected with the loss of a host cell surface molecule essential for the infection process. This reduction in infectivity is the same order of difference between cell lines that synthesize glycosaminoglycans, such as CHO-K1, and HeLa cells that differ in susceptibility by 8-to 10-fold. Other investigators have confirmed the reduction in susceptibility of chlamydiae to these CHO cell mutants but reached different conclusions. Yabushita et al. (24) tested the infectivity of CHO-677 cells using Chlamydia trachomatis serovar L2 and reported a threeto fourfold reduction in infectivity compared to that of CHO-K1 cells. Taraktchoglou et al. (21) found that the infectivity for C. trachomatis serovar L2 was reduced 4.5-fold for CHO-677 cells and 9-fold for CHO-745 cells. Wup...

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Interaction of Chlamydia trachomatis with Mammalian Cells Is Independent of Host Cell Surface Heparan Sulfate Glycosaminoglycans

2006

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“…However, the high concentrations of chlorate required to block Chlamydia infection are toxic to the host cells. Furthermore, F-17 cells deficient in 2-O-sulfation of heparan sulfate show no significant reduction in C. trachomatis infectivity compared with WT cells (32). Attempts at knockdown of the PAPST1 gene have achieved no better than a 20% reduction in 35 SO 4 incorporation, even with a 60% reduction in mRNA levels (25).…”

Section: Discussionmentioning

confidence: 98%

Attachment ofChlamydia trachomatisL2 to host cells requires sulfation

Rosmarin

Carette

Olive

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L2 infection. We identified and confirmed B3GAT3 , B4GALT7 , and SLC35B2 , which encode glucuronosyltransferase I, galactosyltransferase I, and the 3′-phosphoadenosine 5′-phosphosulfate transporter 1, respectively, as important in facilitating Chlamydia infection. Knockout of any of these three genes inhibits Chlamydia attachment. In complementation studies, we found that the introduction of functional copies of these three genes into the null clones restored full susceptibility to Chlamydia infection. The degree of attachment of Chlamydia strongly correlates with the level of sulfation of the host cell, not simply with the amount of heparan sulfate. Thus, other, as-yet unidentified sulfated macromolecules must contribute to infection. These results demonstrate the utility of screens in haploid cells to study interactions of human cells with bacteria. Furthermore, the human null clones generated can be used to investigate the role of heparan sulfate and sulfation in other settings not limited to infectious disease.

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“…Heparatinase treatment of host cells prevented L2 infection and the HS-synthesis deficient CHO [99] cell line was less sensitive to infection.…”

Section: Helamentioning

confidence: 99%

Identification and biochemical characterization of the CHLAMYDIA TRACHOMATIS type III secretion chaperone, SLC1, and its role in the translocation of the invasion-associated effector TARP.

Brinkworth¹

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Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture

Cited by 21 publications

References 30 publications

Interaction of Chlamydia trachomatis with Mammalian Cells Is Independent of Host Cell Surface Heparan Sulfate Glycosaminoglycans

Interaction of Chlamydia trachomatis with Mammalian Cells Is Independent of Host Cell Surface Heparan Sulfate Glycosaminoglycans

Attachment ofChlamydia trachomatisL2 to host cells requires sulfation

Identification and biochemical characterization of the CHLAMYDIA TRACHOMATIS type III secretion chaperone, SLC1, and its role in the translocation of the invasion-associated effector TARP.

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