Interaction of Helicobacter pylori Cell Membrane with Non-Esterified Cholesterol and Other Steroids


Helicobacter pylori performs the unique action of assimilating exogenous non-esterified cholesterol into its cell membrane. This bacterium aggressively incorporates non-esterified cholesterol into the membrane, induces its glucosylation, and uses both non-esterified cholesterol and glucosylated cholesterols as membrane lipid compositions. The reason for this assimilation of non-esterified cholesterol into the cell membrane of H. pylori has eluded investigators for many years. Recent hypotheses posit that the sterol-uptake and sterol-glucosylation contribute to the survival of H. pylori cells in different ways. The incorporation of the non-esterified cholesterol into the cell membrane fortifies the resistance of H. pylori against the antibacterial actions of phosphatidylcholines, antibiotics, and bile salts. In parallel, the glucosylation of the non-esterified cholesterol incorporated into the cell membrane serves H. pylori in two ways. First, it helps the bacterium evade host immune responses, such as phagocytosis by macrophages and activation of antigen-specific T cells. Second, it detoxifies sterols fatal to the bacterium via a novel action of sterol glucosylation recently described in another report from our group. The reluctance of H. pylori to absorb esterified cholesterol remains unexplained. A recent study by our group has demonstrated that the phosphatidylethanolamine (PE) in the outer membrane of H. pylori serves as a steroid-binding lipid the incorporation of non-esterified cholesterol into the membrane. We have also discovered that the myristic acid (C14:0) molecule attached to the PE of this bacterium plays an important role in the selective binding of non-esterified cholesterol but not esterified cholesterol.

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H. Shimomura, K. Hosoda and Y. Hirai, "Interaction of Helicobacter pylori Cell Membrane with Non-Esterified Cholesterol and Other Steroids," Open Journal of Medical Microbiology, Vol. 3 No. 1, 2013, pp. 70-79. doi: 10.4236/ojmm.2013.31011.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. R. Warren and B. Marshall, “Unidentified Curved Bacilli on Gastric Epithelium in Active Chronic Gastritis,” Lancet, Vol. 1, No. 8336, 1983, pp. 1273-1275.
[2] D. Y. Graham, “Helicobacter pylori: Its Epidemiology and Its Role in Duodenal Ulcer Disease,” Journal of Gastroenterology and Hepatology, Vol. 6, No. 2, 1991, pp. 105-113. doi:10.1111/j.1440-1746.1991.tb01448.x
[3] K. Fukase, M. Kato, S. Kikuchi, K. Inoue, N. Uemura, S. Okamoto, S. Terano, K. Amagai, S. Hayashi, M. Asaka and Japan Gast Study Group, “Effect of Eradication of Helicobacter pylori on Incidence of Metachronous Gastric Carcinoma after Endoscopic Resection of Early Gastric Cancer: An Open-Label, Randomised Controlled Trial,” Lancet, Vol. 372, No. 9636, 2008, pp. 392-397. doi:10.1016/S0140-6736(08)61159-9
[4] N. Uemura, S. Okamoto, S. Yamamoto, M. Matsumura, S. Yamaguchi, M. Yamakido, K. Taniyama, N. Sasaki and R. J. Schlemper, “Helicobacter pylori Infection and the Development of Gastric Cancer,” The New England Journal of Medicine, Vol. 345, No. 11, 2001, pp. 829-832. doi:10.1056/NEJMoa001999
[5] D. Forman and the Eurogast Study Group, “An International Association between Helicobacter pylori Infection and Gastric Cancer,” Lancet, Vol. 341, No. 8857, 1993, pp. 1359-1363. doi:10.1016/0140-6736(93)90938-D
[6] A. C. Wotherspoon, C. Ortiz-Hidalgo, M. R. Falzon and P. G. Isaacson, “Helicobacter pylori-Associated Gastritis and Primary B-Cell Gastric Lymphoma,” Lancet, Vol. 338, No. 8776, 1991, pp. 1175-1176. doi:10.1016/0140-6736(91)92035-Z
[7] R. M. Peek Jr. and M. J. Blaser, “Helicobacter pylori and Gastrointestinal Tract Adenocarcinomas,” Nature Reviews Cancer, Vol. 2, No. 1, 2002, pp. 28-37. doi:10.1038/nrc703
[8] R. M. Peek Jr. and J. E. Crabtree, “Helicobacter Infection and Gastric Neoplasia,” Journal of Pathology, Vol. 208, No. 2, 2006, pp. 233-248. doi:10.1002/path.1868
[9] M. Stolte, E. Bayerdorffer, A. Morgner, B. Alpen, T. Wundish, C. Thiede and A. Neubauer, “Helicobacter and Gastric MALT Lymphoma,” Gut, Vol. 50, No. 3, 2002, pp. III19-III24. doi:10.1136/gut.50.suppl_3.iii19
[10] M. Haque, Y. Hirai, K. Yokota and K. Oguma, “Steryl Glucosides: A Characteristic Feature of the Helicobacter spp.?” Journal of Bacteriology, Vol. 177, No. 18, 1995, pp. 5334-5337.
[11] M. Haque, Y. Hirai, K. Yokota, N. Mori, I. Jahan, H. Ito, H. Hotta, I. Yano, Y. Kanemasa and K. Oguma, “Lipid Profile of Helicobacter spp.: Presence of Cholesteryl Glucoside as a Characteristic Feature,” Journal of Bacteriology, Vol. 178, No. 7, 1996, pp. 2065-2070.
[12] B. P. Livermore, R. F. Bey and R. C. Johnson, “Lipid Metabolism of Borrelia hermsii,” Infection and Immunity, Vol. 20, No. 1, 1978, pp. 215-220.
[13] W. R. Mayberry and P. F. Smith, “Structures and Properties of Acyl Diglucosylcholesterol and Galactofuranosyl Diacylglycerol from Acholeplasma axanthum,” Biochimica et Biophysica Acta, Vol. 752, No. 3, 1983, pp. 434-443. doi:10.1016/0005-2760(83)90273-4
[14] K. R. Patel, P. F. Smith and W. R. Mayberry, “Comparison of Lipids from Spiroplasma citri and Corn Stunt spiroplasma,” Journal of Bacteriology, Vol. 136, No. 2, 1978, pp. 829-831.
[15] P. F. Smith, “Biosynthesis of Cholesteryl Glucoside by Mycoplasma gallinarum,” Journal of Bacteriology, Vol. 108, No. 3, 1971, pp. 986-991.
[16] Y. K. Kim, Y. Wang, Z. M. Liu and P. E. Kolattukudy, “Identification of a Hard Surface Contact-Induced Gene in Colletotrichum gloeosporioides Conidia as a Sterol Glucosyltransferase, a Novel Fungi Virulence Factor,” Plant Journal, Vol. 30, No. 2, 2002, pp. 177-187. doi:10.1046/j.1365-313X.2002.01284.x
[17] M. Oku, D. Warnecke, T. Noda, F. Müller, E. Heinz, H. Mukaiyama, N. Kato and Y. Sakai, “Peroxisome Degradation Requires Catalytically Active Sterol Glucosyltransferase with a GRAM Domain,” EMBO Journal, Vol. 22, No. 13, 2003, pp. 3231-3241. doi:10.1093/emboj/cdg331
[18] L. Peng, Y. Kawagoe, P. Hogan and D. Delmer, “Sitosterol-β-Glucoside as Primer for Cellulose Synthesis in Plants,” Science, Vol. 295, No. 5552, 2002, pp. 147-150. doi:10.1126/science.1064281
[19] D. C. Warnecke and E. Heinz, “Purification of a Membrane-Bound UDP-Glucose: Sterol-D-Glucosyltransferase Based on Its Solubility in Diethyl Ether,” Plant Physiology, Vol. 105, No. 4, 1994, pp. 1067-1073.
[20] D. C. Warnecke, M. Baltrusch, F. Buck, F. P. Wolter and E. Heinz, “UDP-Glucose:Sterol Glucosyltransferase: Cloning and Functional Expression in Escherichia coli,” Plant Molecular Biology, Vol. 35, No. 5, 1997, pp. 597-603. doi:10.1023/A:1005806119807
[21] D. Warnecke, R. Erdmann, A. Fahl, B. Hube, F. Müller, T. Zank, U. Z?hringer and E. Heinz, “Cloning and Functional Expression of UGT Gene Encoding Sterol Glucosyltransferase from Saccharomyces cerevisiae, Candida albicans, Pichia pastoris, and Dictyostelium discoideum,” Journal of Biological Chemistry, Vol. 274, No. 19, 1999, pp. 13048-13059. doi:10.1074/jbc.274.19.13048
[22] G. Stübs, V. Fingerle, B. Wilske, U. B. Gobel, U. Z?hringer, R. R. Schumann and N. W. Schr?der, “Acylated Cholesteryl Galactosides Are Specific Antigens of Borrelia Causing Lyme Disease and Frequency Induce Antibodies in Late Stage of Disease,” Journal of Biological Chemistry, Vol. 284, No. 20, 2009, pp. 13326-13334. doi:10.1074/jbc.M809575200
[23] G. Ben-Menachem, J. Kubler-Kielb, B. Coxon, A. Yergey and R. Schneerson, “A Newly Discovered Cholesteryl Galactoside from Borrelia burgdorferi,” Proceedings of the National Academy of Sciences of USA, Vol. 100, No. 13, 2003, pp. 7193-7918. doi:10.1073/pnas.1232451100
[24] N. W. Schr?der, U. Schombel, H. Heine, U. B. Gobel, U. Z?hringer and R. R. Schumann, “Acylated Cholesteryl Galactoside as a Novel Immunogenic Motif in Borrelia burgdorferi sensu stricto,” Journal of Biological Chemistry, Vol. 278, No. 36, 2003, pp. 33645-33653. doi:10.1074/jbc.M305799200
[25] A. H. Lebrun, C. Wunder, J. Hildebrand, Y. Churin, U. Z?hringer, B. Lindner, T. F. Mayer, E. Heinz and D. Warnecke, “Cloning of a Cholesterol-α-Glucosyltransferase from Helicobacter pylori,” Journal of Biological Chemistry, Vol. 281, No. 38, 2006, pp. 27765-27772. doi:10.1074/jbc.M603345200
[26] Y. Hirai, M. Haque, T. Yoshida, K. Yokota, T. Yasuda and K. Oguma, “Unique Cholesteryl Glucosides in Helicobacter pylori: Composition and Structural Analysis,” Journal of Bacteriology, Vo. 177, No. 18, 1995, pp. 5327-5333.
[27] H. Shimomura, K. Hosoda, S. Hayashi, K. Yokota, K. Oguma and Y. Hirai, “Steroids Mediate Resistance to the Bactericidal Effect of Phosphatidylcholines against Helicobacter pylori,” FEMS Microbiology Letters, Vol. 301, No. 1, 2009, pp. 84-94. doi:10.1111/j.1574-6968.2009.01807.x
[28] C. Wunder, Y. Churin, F. Winau, D. Warnecke, M. Vieth, B. Lindner, U. Z?hringer, H. J. Mollenkopf, E. Heinz and T. F. Meyer, “Cholesterol Glucosylation Promotes Immune Evasion by Helicobacter pylori,” Nature Medicine, Vol. 12, No. 9, 2006, pp. 1030-1038. doi:10.1038/nm1480
[29] K. Berstad, A. J. Berstad, R. Sj?dahl, R. Weberg and A. Berstad, “Eosinophil Cationic Protein and Phospholipase A2 Activity in Human Gastric Juice with Emphasis on Helicobacter pylori Status and Effects of Antacids,” Scandinavian Journal of Gastroenterology, Vol. 27, No. 12, 1992, pp. 1011-1017. doi:10.3109/00365529209028131
[30] T. Orihara, H. Wakabayashi, A. Nakaya, K. Fukuta, S. Makimoto, K. Naganuma, A. Entani and A. Watanave, “Effect of Helicobacter pylori Eradication on Gastric Mucosal Phospholipid Content and Its Fatty Acid Composition,” Journal of Gastroenterology and Hepatology, Vol. 16, No. 3, 2001, pp. 269-275. doi:10.1046/j.1440-1746.2001.02440.x
[31] D. J. McGee, A. E. George, E. A. Trainor, K. E. Horton, E. Hildebrandt and T. L. Testerman, “Cholesterol Enhances Helicobacter pylori Resistance to Antibiotics and LL-37,” Antimicrobial Agents and Chemotherapy, Vol. 55, No. 6, 2011, pp. 2897-2904. doi:10.1128/AAC.00016-11
[32] E. A. Trainor, K. E. Horton, P. E. Savage, T. L. Testerman and D. J. McGee, “Role of the HefC Efflux Pump in Helicobacter pylori Cholesterol-Dependent Resistance to Ceragenins and Bile Salts,” Infection and Immunity, Vol. 79, No. 1, 2011, pp. 88-97. doi:10.1128/IAI.00974-09
[33] N. B. Javitt, Y. C. Lee, C. Shimizu, H. Fuda and C. A. Strott, “Cholesterol and Hydroxycholesterol Sulfotransferase: Identification, Distinction from Dehydroepiandrosterone Sulfotransferase, and Differential Tissue Expression,” Endocrinology, Vol. 142, No. 7, 2001, pp. 2978-2984. doi:10.1210/en.142.7.2978
[34] Y. Miki, T. Nakata, T. Suzuki, A. D. Darnel, T. Moriya, C. Kaneko, K. Hidaka, Y. Shiotsu, H. Kusaka and H. Sasano, “Systematic Distribution of Steroid Sulfatase and Estrogen Sulfotransferase in Human Adult and Fetal Tissues,” Journal of Clinical Endocrinology & Metabolism, Vol. 87, No. 12, 2002, pp. 5760-5768. doi:10.1210/jc.2002-020670
[35] J. Takeyama, T. Suzuki, G. Hirasawa, Y. Muramatsu, H. Nagura, K. Iinuma, J. Nakamura, K. I. Kimura, M. Yoshihama, N. Harada, S. Andersson and H. Sasano, “17βHydroxysteroid Dehydrogenase Type 1 and 2 Expression in the Human Fetus,” Journal of Clinical Endocrinology & Metabolism, Vol. 85, No. 1, 2000, pp. 410-416. doi:10.1210/jc.85.1.410
[36] D. Turgeon, J. S. Carrier, E. Levesque, D. W. Hum and A. Belanger, “Relative Enzymatic Activity, Protein Stability, and Tissue Distribution of Human Steroid-Metabolizing UGT2B Subfamily Members,” Endocrinology, Vol. 142, No. 2, 2001, pp. 778-787. doi:10.1210/en.142.2.778
[37] A. Kominea, P. A. Konstantinopoulos, N. Kapranos, G. Vondoros, M. Gkermpesi, P. Andricopoulos, S. Artelaris, S. Savva, I. Varakis, G. Sotiropoulou-Bonikou and A. G. Papavassiliou, “Androgen Receptor (AR) Expression Is an Independent Unfavorable Prognostic Factor in Gastric Cancer,” Journal of Cancer Research and Clinical Oncology, Vol. 130, No. 5, 2004, pp. 253-258. doi:10.1007/s00432-003-0531-x
[38] S. Matsuyama, Y. Ohkura, H. Eguchi, Y. Kobayashi, K. Akagi, K. Uchida, K. Nakachi, J. A. Gustafsson and S. Hayashi, “Estrogen Receptor β Is Expressed in Human Stomach Adenocarcinoma,” Journal of Cancer Research and Clinical Oncology, Vol. 128, No. 6, 2002, pp. 219-324. doi:10.1007/s00432-002-0336-3
[39] N. Takano, N. Iizuka, S. Hazama, S. Yoshino, A. Tangoku and M. Oka, “Expression of Estrogen Receptor-α and -β mRNAs in Human Gastric Cancer,” Cancer Letter, Vol. 176, No. 2, 2002, pp. 129-135. doi:10.1016/S0304-3835(01)00739-X
[40] K. Hosoda, H. Shimomura, S. Hayashi, K. Yokota, K. Oguma and Y. Hirai, “Anabolic Utilization of Steroid Hormones in Helicobacter pylori,” FEMS Microbiology Letters, Vol. 297, No. 2, 2009, pp. 173-179. doi:10.1111/j.1574-6968.2009.01685.x
[41] K. Hosoda, H. Shimomura, S. Hayashi, K. Yokota and Y. Hirai, “Steroid Hormones as Bactericidal Agents to Helicobacter pylori,” FEMS Microbiology Letters, Vol. 318, No. 1, 2011, pp. 68-75. doi:10.1111/j.1574-6968.2011.02239.x
[42] H. Shimomura, S. Hayashi, K. Yokota, K. Oguma and Y. Hirai, “Alteration in the Composition of Cholesteryl Glucosides and Other Lipids in Helicobacter pylori Undergoing Morphological Change from Spiral to Coccoid Form,” FEMS Microbiology Letters, Vol. 237, No. 2, 2004, pp. 407-413.
[43] H. Shimomura, K. Hosoda, S. Hayashi, K. Yokota and Y. Hirai, “Phosphatidylethanolamine of Helicobacter pylori Functions as a Steroid-Binding Lipid in the Assimilation of Free Cholesterol and 3β-Hydroxl Steroids into the Bacterial Cell Membrane,” Journal of Bacteriology, Vol. 194, No. 10, 2012, pp. 2658-2667. doi:10.1128/JB.00105-12
[44] A. Amine, K. S. Saloua, M. Mouadh, E. I. M. Alya and L. Ahmed, “The Absence of the ‘GATC-Binding Protein SegA’ Affect DNA Replication in Salmonella enterica Serovar Typhimurium,” In: J. Kusic-Tisma, Ed., DNA Replication and Related Cellular Process, InTech, Rijeka, 2011. http//
[45] J. K. Dunnick and W. M. O’Leary, “Correlation of Bacterial Lipid Composition with Antibiotic Resistance,” J. Bacteriol., Vol. 101, No. 3, 1970, pp. 892-900.
[46] D. B. Kearns, J. Robinson and L. J. Shimkets, “Pseudomonas aeruginosa exhibits directed twitching motility up phosphatidylethanolamine gradients,” Journal of Bacteriology, Vol. 183, No. 2, 2001, pp. 763-767. doi:10.1128/JB.183.2.763-767.2001
[47] A. Shokri and G. Larsson, “Characterisation of the Escherichia coli Membrane Structure and Function during Fed Batch Cultivation,” Microbial Cell Factories, Vol. 3, 2004, pp. 1-9. doi:10.1186/1475-2859-3-1
[48] H. Shimomura, K. Hosoda, D. J. McGee, S. Hayashi, K. Yokota and Y. Hirai, “Detoxification of 7-Dehydrocholesterol Fatal to Helicobacter pylori Is a Novel Role of Cholesterol Glucosylation,” Journal of Bacteriology, Vol. 195, No. 2, 2013, pp. 359-367. doi:10.1128/JB.01495-12
[49] N. B. Javitt, “Oxysterols: A New Class of Steroids with Autocrine and Paracrine Functions,” Trends in Endocrinology & Metabolism, Vol. 15, No. 8, 2004, pp. 393-397.
[50] G. S. Tint, M. Irons, E. R. Elias, A. K. Batta, R. Frieden, T. S. Chen and G. Salen, “Defective Cholesterol Biosynthesis Associated with the Smith-Lemli-Opitz Syndrome,” The New England Journal of Medicine, Vol. 330, No. 2, 1994, pp. 107-113. doi:10.1056/NEJM199401133300205
[51] I. Bj?rkhem, L. Starck, U. Andersson, D. Lütjohann, S. von Bahr, I. Pikuleva, A. Babiker and U. Diczfalusy, “Oxysterols in the Circulation of Patients with the SmithLemli-Opitz Syndrome: Abnormal Levels of 24Sand 27-Hydroxycholesterol,” Journal of Lipid Research, Vol. 42, No. 3, 2001, pp. 366-371.
[52] P. E. Jira, J. G. N. De Jong, F. S. M. Janssen-Zijlstra, U. Wendel and R. A. Wevers, “Pitfalls in Measuring Plasma Cholesterol in the Smith-Lemli-Opitz Syndrome,” Clinical Chemistry, Vol. 43, No. 1, 1997, pp. 129-133.
[53] L. S. Merkens, W. E. Connor, L. M. Linck, D. S. Lin, D. P. Flavell and R. D. Steiner, “Effects of Dietary Cholesterol on Plasma Lipoproteins in Smith-Lemli-Opitz Syndrome,” Pediatric Research, Vol. 56, No. 5, 2004, pp. 726-732. doi:10.1203/01.PDR.0000141522.14177.4F
[54] E. T. Rietschel, T. Kirikae, F. U. Schade, U. Mamat, G. Schmidt, H. Loppnow, A. J. Ulmer, U. Z?hringer, U. Seydel, F. D. Padova, M. Schreier and H. Brade, “Bacterial Endotoxin: Molecular Relationship of Structure to Activity and Function,” FESEB Journal, Vol. 8, No. 2, 1994, pp. 217-225.
[55] L. Guo, K. B. Lim, J. S. Gunn, B. Bainbridge, R. P. Darveau, M. Hackett and S. I. Miller, “Regulation of Lipid A Modification by Salmonella typhimurium Virulence Genes phoP-phoQ,” Science, Vol. 276, No. 5310, 1997, pp. 250-253. doi:10.1126/science.276.5310.250
[56] C. L. Hall and R. S. Munford, “Enzymatic Deacylation of the Lipid A Moiety of Salmonella typhimurium Lipopolysaccharides by Human Neutrophils,” Proceedings of the National Academy of Sciences of USA, Vol. 80, No. 21, 1983, pp. 6671-6675. doi:10.1073/pnas.80.21.6671
[57] C. M. Stead, A. Beasley, R. J. Cotter and M. S. Trent, “Deciphering the Unusual Acylation Pattern of Helicobacter pylori Lipid A,” Journal of Bacteriology, Vol. 190, No. 21, 2008, pp. 7012-7021. doi:10.1128/JB.00667-08

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