Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection

Kim JH, Chan C, Elwell C, Singer MS, Dierks T, Lemjabbar-Alaoui H, Rosen SD, Engel JN (2013)
Cellular Microbiology 15(9): 1560-1571.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Kim, J H; Chan, C; Elwell, C; Singer, M S; Dierks, ThomasUniBi; Lemjabbar-Alaoui, H; Rosen, S D; Engel, J N
Abstract / Bemerkung
The first step in attachment of Chlamydia to host cells is thought to involve reversible binding to host heparan sulfate proteoglycans (HSPGs), polymers of variably sulfated repeating disaccharide units coupled to diverse protein backbones. However, the key determinants of HSPG structure that are involved in Chlamydia binding are incompletely defined. A previous genome-wide Drosophila RNAi screen suggested that the level of HSPG 6-O sulfation rather than the identity of the proteoglycan backbone maybe a critical determinant for binding. Here, we tested in mammalian cells whether SULF1 or SULF2, human endosulfatases, which remove 6-O sulfates from HSPGs, modulate Chlamydia infection. Ectopic expression of SULF1 or SULF2 in HeLa cells, which decreases cell surface HSPG sulfation, diminished C. muridarum binding and decreased vacuole formation. ShRNA depletion of endogenous SULF2 in a cell line that primarily expresses SULF2 augmented binding and increased vacuole formation. C. muridarum infection of diverse cell lines resulted indownregulation of SULF2 mRNA. In a murine model of acute pneumonia, mice genetically deficient in both endosulfatases or in SULF2 alone demonstrated increased susceptibility to C. muridarum lung infection. Collectively, these studies demonstrate that the level of HSPG 6-O sulfation is a critical determinant of C. muridarum infection in vivo and that 6-O endosulfatases are previously unappreciated modulators of microbial pathogenesis.
Cellular Microbiology
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Kim JH, Chan C, Elwell C, et al. Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cellular Microbiology. 2013;15(9):1560-1571.
Kim, J. H., Chan, C., Elwell, C., Singer, M. S., Dierks, T., Lemjabbar-Alaoui, H., Rosen, S. D., et al. (2013). Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cellular Microbiology, 15(9), 1560-1571. doi:10.1111/cmi.12133
Kim, J H, Chan, C, Elwell, C, Singer, M S, Dierks, Thomas, Lemjabbar-Alaoui, H, Rosen, S D, and Engel, J N. 2013. “Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection”. Cellular Microbiology 15 (9): 1560-1571.
Kim, J. H., Chan, C., Elwell, C., Singer, M. S., Dierks, T., Lemjabbar-Alaoui, H., Rosen, S. D., and Engel, J. N. (2013). Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cellular Microbiology 15, 1560-1571.
Kim, J.H., et al., 2013. Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cellular Microbiology, 15(9), p 1560-1571.
J.H. Kim, et al., “Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection”, Cellular Microbiology, vol. 15, 2013, pp. 1560-1571.
Kim, J.H., Chan, C., Elwell, C., Singer, M.S., Dierks, T., Lemjabbar-Alaoui, H., Rosen, S.D., Engel, J.N.: Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection. Cellular Microbiology. 15, 1560-1571 (2013).
Kim, J H, Chan, C, Elwell, C, Singer, M S, Dierks, Thomas, Lemjabbar-Alaoui, H, Rosen, S D, and Engel, J N. “Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection”. Cellular Microbiology 15.9 (2013): 1560-1571.

3 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Targeting heparin and heparan sulfate protein interactions.
Weiss RJ, Esko JD, Tor Y., Org Biomol Chem 15(27), 2017
PMID: 28653068
Chlamydia cell biology and pathogenesis.
Elwell C, Mirrashidi K, Engel J., Nat Rev Microbiol 14(6), 2016
PMID: 27108705
Characterization of the interaction between the chlamydial adhesin OmcB and the human host cell.
Fechtner T, Stallmann S, Moelleken K, Meyer KL, Hegemann JH., J Bacteriol 195(23), 2013
PMID: 24056107

54 References

Daten bereitgestellt von Europe PubMed Central.

SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation.
Ai X, Kitazawa T, Do AT, Kusche-Gullberg M, Labosky PA, Emerson CP Jr., Development 134(18), 2007
PMID: 17720696
Functions of cell surface heparan sulfate proteoglycans.
Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M., Annu. Rev. Biochem. 68(), 1999
PMID: 10872465
Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis.
Caldwell HD, Kromhout J, Schachter J., Infect. Immun. 31(3), 1981
PMID: 7228399
Chlamydia pneumoniae and atherosclerosis.
Campbell LA, Kuo CC., Semin Respir Infect 18(1), 2003
PMID: 12652454
Identification of SULF2 as a novel transcriptional target of p53 by use of integrated genomic analyses.
Chau BN, Diaz RL, Saunders MA, Cheng C, Chang AN, Warrener P, Bradshaw J, Linsley PS, Cleary MA., Cancer Res. 69(4), 2009
PMID: 19190338
Structural requirements of heparin binding to Chlamydia trachomatis.
Chen JC, Zhang JP, Stephens RS., J. Biol. Chem. 271(19), 1996
PMID: 8626658
Microbial subversion of heparan sulfate proteoglycans.
Chen Y, Gotte M, Liu J, Park PW., Mol. Cells 26(5), 2008
PMID: 18799929
Chlamydia trachomatis pneumonia in the immune, athymic and normal BALB mouse.
Coalson JJ, Winter VT, Bass LB, Schachter J, Grubbs BG, Williams DM., Br J Exp Pathol 68(3), 1987
PMID: 3040067
Recent insights into the mechanisms of Chlamydia entry.
Dautry-Varsat A, Subtil A, Hackstadt T., Cell. Microbiol. 7(12), 2005
PMID: 16309458
Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase.
Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CP Jr., Science 293(5535), 2001
PMID: 11533491
RNA interference screen identifies Abl kinase and PDGFR signaling in Chlamydia trachomatis entry.
Elwell CA, Ceesay A, Kim JH, Kalman D, Engel JN., PLoS Pathog. 4(3), 2008
PMID: 18369471
Molecular diversity of heparan sulfate.
Esko JD, Lindahl U., J. Clin. Invest. 108(2), 2001
PMID: 11457867
Enhanced virulence of Chlamydia muridarum respiratory infections in the absence of TLR2 activation.
He X, Nair A, Mekasha S, Alroy J, O'Connell CM, Ingalls RR., PLoS ONE 6(6), 2011
PMID: 21695078
Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival.
Holst CR, Bou-Reslan H, Gore BB, Wong K, Grant D, Chalasani S, Carano RA, Frantz GD, Tessier-Lavigne M, Bolon B, French DM, Ashkenazi A., PLoS ONE 2(6), 2007
PMID: 17593974
Direct detection of HSulf-1 and HSulf-2 activities on extracellular heparan sulfate and their inhibition by PI-88.
Hossain MM, Hosono-Fukao T, Tang R, Sugaya N, van Kuppevelt TH, Jenniskens GJ, Kimata K, Rosen SD, Uchimura K., Glycobiology 20(2), 2009
PMID: 19822709
Entry mechanisms of Chlamydia trachomatis into non-phagocytic cells
Hybiske K, Stephens RS., 2007
HSulf-1 modulates FGF2- and hypoxia-mediated migration and invasion of breast cancer cells.
Khurana A, Liu P, Mellone P, Lorenzon L, Vincenzi B, Datta K, Yang B, Linhardt RJ, Lingle W, Chien J, Baldi A, Shridhar V., Cancer Res. 71(6), 2011
PMID: 21266348
Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection.
Kim JH, Jiang S, Elwell CA, Engel JN., PLoS Pathog. 7(10), 2011
PMID: 21998584
Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer.
Lai J, Chien J, Staub J, Avula R, Greene EL, Matthews TA, Smith DI, Kaufmann SH, Roberts LR, Shridhar V., J. Biol. Chem. 278(25), 2003
PMID: 12686563
The tumor suppressor function of human sulfatase 1 (SULF1) in carcinogenesis.
Lai JP, Sandhu DS, Shire AM, Roberts LR., J Gastrointest Cancer 39(1-4), 2008
PMID: 19373441
Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma.
Lai JP, Sandhu DS, Yu C, Han T, Moser CD, Jackson KK, Guerrero RB, Aderca I, Isomoto H, Garrity-Park MM, Zou H, Shire AM, Nagorney DM, Sanderson SO, Adjei AA, Lee JS, Thorgeirsson SS, Roberts LR., Hepatology 47(4), 2008
PMID: 18318435
Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity.
Lamanna WC, Baldwin RJ, Padva M, Kalus I, Ten Dam G, van Kuppevelt TH, Gallagher JT, von Figura K, Dierks T, Merry CL., Biochem. J. 400(1), 2006
PMID: 16901266
The heparanome--the enigma of encoding and decoding heparan sulfate sulfation.
Lamanna WC, Kalus I, Padva M, Baldwin RJ, Merry CL, Dierks T., J. Biotechnol. 129(2), 2007
PMID: 17337080
Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis.
Lemjabbar-Alaoui H, van Zante A, Singer MS, Xue Q, Wang YQ, Tsay D, He B, Jablons DM, Rosen SD., Oncogene 29(5), 2009
PMID: 19855436
Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer.
Li J, Kleeff J, Abiatari I, Kayed H, Giese NA, Felix K, Giese T, Buchler MW, Friess H., Mol. Cancer 4(1), 2005
PMID: 15817123
Gene trap disruption of the mouse heparan sulfate 6-O-endosulfatase gene, Sulf2.
Lum DH, Tan J, Rosen SD, Werb Z., Mol. Cell. Biol. 27(2), 2006
PMID: 17116694
Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis.
Lundin L, Larsson H, Kreuger J, Kanda S, Lindahl U, Salmivirta M, Claesson-Welsh L., J. Biol. Chem. 275(32), 2000
PMID: 10816596

Mandell GL, Bennett JE, Dolin R., 2010
Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans.
Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD., J. Biol. Chem. 277(51), 2002
PMID: 12368295
Interaction of chlamydiae and host cells in vitro.
Moulder JW., Microbiol. Rev. 55(1), 1991
PMID: 2030670
Chlamydia trachomatis pulmonary infection induces greater inflammatory pathology in immunoglobulin A deficient mice.
Murthy AK, Sharma J, Coalson JJ, Zhong G, Arulanandam BP., Cell. Immunol. 230(1), 2004
PMID: 15541719
Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways.
Otsuki S, Hanson SR, Miyaki S, Grogan SP, Kinoshita M, Asahara H, Wong CH, Lotz MK., Proc. Natl. Acad. Sci. U.S.A. 107(22), 2010
PMID: 20479257
Heparan sulfate sulfatase SULF2 regulates PDGFRα signaling and growth in human and mouse malignant glioma.
Phillips JJ, Huillard E, Robinson AE, Ward A, Lum DH, Polley MY, Rosen SD, Rowitch DH, Werb Z., J. Clin. Invest. 122(3), 2012
PMID: 22293178
Strain and virulence diversity in the mouse pathogen Chlamydia muridarum.
Ramsey KH, Sigar IM, Schripsema JH, Denman CJ, Bowlin AK, Myers GA, Rank RG., Infect. Immun. 77(8), 2009
PMID: 19470744
Chlamydial diseases
Rank RG., 2006
Chlamydia-dependent biosynthesis of a heparan sulphate-like compound in eukaryotic cells.
Rasmussen-Lathrop SJ, Koshiyama K, Phillips N, Stephens RS., Cell. Microbiol. 2(2), 2000
PMID: 11207570
Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development.
Ratzka A, Kalus I, Moser M, Dierks T, Mundlos S, Vortkamp A., Dev. Dyn. 237(2), 2008
PMID: 18213582
Attachment of Chlamydia trachomatis L2 to host cells requires sulfation
Rosmarin DM, Carette JE, Olive AJ, Starnbach MN, Brummelkamp TR, Ploegh HL., 2012
Distinct role of 2-O-, N-, and 6-O-sulfate groups of heparin in the formation of the ternary complex with basic fibroblast growth factor and soluble FGF receptor-1.
Rusnati M, Coltrini D, Caccia P, Dell'Era P, Zoppetti G, Oreste P, Valsasina B, Presta M., Biochem. Biophys. Res. Commun. 203(1), 1994
PMID: 8074689
A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry.
Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, Esko JD, Cohen GH, Eisenberg RJ, Rosenberg RD, Spear PG., Cell 99(1), 1999
PMID: 10520990
A recombinant Chlamydia trachomatis major outer membrane protein binds to heparan sulfate receptors on epithelial cells.
Su H, Raymond L, Rockey DD, Fischer E, Hackstadt T, Caldwell HD., Proc. Natl. Acad. Sci. U.S.A. 93(20), 1996
PMID: 8855323
Functional consequences of the subdomain organization of the sulfs.
Tang R, Rosen SD., J. Biol. Chem. 284(32), 2009
PMID: 19520866
Role of heparan sulfate in sexually transmitted infections
Tiwari V, Maus E, Sigar IM, Ramsey KH, Shukla D., 2012
Heparan sulfate-like glycosaminoglycan is a cellular receptor for Chlamydia pneumoniae.
Wuppermann FN, Hegemann JH, Jantos CA., J. Infect. Dis. 184(2), 2001
PMID: 11424015
Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture.
Yabushita H, Noguchi Y, Habuchi H, Ashikari S, Nakabe K, Fujita M, Noguchi M, Esko JD, Kimata K., Glycobiology 12(5), 2002
PMID: 12070077
Transforming growth factor-beta1 induces heparan sulfate 6-O-endosulfatase 1 expression in vitro and in vivo.
Yue X, Li X, Nguyen HT, Chin DR, Sullivan DE, Lasky JA., J. Biol. Chem. 283(29), 2008
PMID: 18503048
N- and 6-O-sulfated heparan sulfates mediate internalization of coxsackievirus B3 variant PD into CHO-K1 cells.
Zautner AE, Jahn B, Hammerschmidt E, Wutzler P, Schmidtke M., J. Virol. 80(13), 2006
PMID: 16775350
Mechanism of C. trachomatis attachment to eukaryotic host cells.
Zhang JP, Stephens RS., Cell 69(5), 1992
PMID: 1591780

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