This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laffitte, B. A.
Right arrow Articles by Tontonoz, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laffitte, B. A.
Right arrow Articles by Tontonoz, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2001, p. 7558-7568, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7558-7568.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Autoregulation of the Human Liver X Receptor alpha  Promoter

Bryan A. Laffitte,1 Sean B. Joseph,2 Robert Walczak,1 Liming Pei,2 Damien C. Wilpitz,1 Jon L. Collins,3 and Peter Tontonoz1,2,*

Howard Hughes Medical Institute1 and Department of Pathology and Laboratory Medicine,2 University of California, Los Angeles, California 90095-1662, and Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina 27709-33983

Received 17 April 2001/Returned for modification 29 June 2001/Accepted 28 August 2001

Previous work has implicated the nuclear receptors liver X receptor alpha  (LXRalpha ) and LXRbeta in the regulation of macrophage gene expression in response to oxidized lipids. Macrophage lipid loading leads to ligand activation of LXRs and to induction of a pathway for cholesterol efflux involving the LXR target genes ABCA1 and apoE. We demonstrate here that autoregulation of the LXRalpha gene is an important component of this lipid-inducible efflux pathway in human macrophages. Oxidized low-density lipoprotein, oxysterols, and synthetic LXR ligands induce expression of LXRalpha mRNA in human monocyte-derived macrophages and human macrophage cell lines but not in murine peritoneal macrophages or cell lines. This is in contrast to peroxisome proliferator-activated receptor gamma  (PPARgamma )-specific ligands, which stimulate LXRalpha expression in both human and murine macrophages. We further demonstrate that LXR and PPARgamma ligands cooperate to induce LXRalpha expression in human but not murine macrophages. Analysis of the human LXRalpha promoter led to the identification of multiple LXR response elements. Interestingly, the previously identified PPAR response element (PPRE) in the murine LXRalpha gene is not conserved in humans; however, a different PPRE is present in the human LXR 5'-flanking region. These results have implications for cholesterol metabolism in human macrophages and its potential to be regulated by synthetic LXR and/or PPARgamma ligands. The ability of LXRalpha to regulate its own promoter is likely to be an integral part of the macrophage physiologic response to lipid loading.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, UCLA School of Medicine, Box 951662, Los Angeles, CA 90095-1662. Phone: (310) 206-4546. Fax: (310) 267-0382. E-mail: ptontonoz{at}mednet.ucla.edu.

Molecular and Cellular Biology, November 2001, p. 7558-7568, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7558-7568.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lakomy, D., Rebe, C., Sberna, A.-L., Masson, D., Gautier, T., Chevriaux, A., Raveneau, M., Ogier, N., Nguyen, A. T., Gambert, P., Grober, J., Bonnotte, B., Solary, E., Lagrost, L. (2009). Liver X Receptor-Mediated Induction of Cholesteryl Ester Transfer Protein Expression Is Selectively Impaired in Inflammatory Macrophages. Arterioscler. Thromb. Vasc. Bio. 29: 1923-1929 [Abstract] [Full Text]  
  • Rebe, C., Raveneau, M., Chevriaux, A., Lakomy, D., Sberna, A.-L., Costa, A., Bessede, G., Athias, A., Steinmetz, E., Lobaccaro, J. M. A., Alves, G., Menicacci, A., Vachenc, S., Solary, E., Gambert, P., Masson, D. (2009). Induction of Transglutaminase 2 by a Liver X Receptor/Retinoic Acid Receptor {alpha} Pathway Increases the Clearance of Apoptotic Cells by Human Macrophages. Circ. Res. 105: 393-401 [Abstract] [Full Text]  
  • Marathe, C., Bradley, M. N., Hong, C., Chao, L., Wilpitz, D., Salazar, J., Tontonoz, P. (2009). Preserved glucose tolerance in high-fat-fed C57BL/6 mice transplanted with PPAR{gamma}-/-, PPAR{delta}-/-, PPAR{gamma}{delta}-/-, or LXR{alpha}{beta}-/- bone marrow. J. Lipid Res. 50: 214-224 [Abstract] [Full Text]  
  • Hozoji, M., Munehira, Y., Ikeda, Y., Makishima, M., Matsuo, M., Kioka, N., Ueda, K. (2008). Direct Interaction of Nuclear Liver X Receptor-{beta} with ABCA1 Modulates Cholesterol Efflux. J. Biol. Chem. 283: 30057-30063 [Abstract] [Full Text]  
  • Hoon Lee, J., Gong, H., Khadem, S., Lu, Y., Gao, X., Li, S., Zhang, J., Xie, W. (2008). Androgen Deprivation by Activating the Liver X Receptor. Endocrinology 149: 3778-3788 [Abstract] [Full Text]  
  • Stayrook, K. R., Rogers, P. M., Savkur, R. S., Wang, Y., Su, C., Varga, G., Bu, X., Wei, T., Nagpal, S., Liu, X. S., Burris, T. P. (2008). Regulation of Human 3{alpha}-Hydroxysteroid Dehydrogenase (AKR1C4) Expression by the Liver X Receptor {alpha}. Mol. Pharmacol. 73: 607-612 [Abstract] [Full Text]  
  • Herzog, B., Hallberg, M., Seth, A., Woods, A., White, R., Parker, M. G. (2007). The Nuclear Receptor Cofactor, Receptor-Interacting Protein 140, Is Required for the Regulation of Hepatic Lipid and Glucose Metabolism by Liver X Receptor. Mol. Endocrinol. 21: 2687-2697 [Abstract] [Full Text]  
  • Qiu, G., Hill, J. S. (2007). Atorvastatin decreases lipoprotein lipase and endothelial lipase expression in human THP-1 macrophages. J. Lipid Res. 48: 2112-2122 [Abstract] [Full Text]  
  • Ludtke, A., Buettner, J., Wu, W., Muchir, A., Schroeter, A., Zinn-Justin, S., Spuler, S., Schmidt, H. H.-J., Worman, H. J. (2007). Peroxisome Proliferator-Activated Receptor-{gamma} C190S Mutation Causes Partial Lipodystrophy. J. Clin. Endocrinol. Metab. 92: 2248-2255 [Abstract] [Full Text]  
  • Traves, P. G., Hortelano, S., Zeini, M., Chao, T.-H., Lam, T., Neuteboom, S. T., Theodorakis, E. A., Palladino, M. A., Castrillo, A., Bosca, L. (2007). Selective Activation of Liver X Receptors by Acanthoic Acid-Related Diterpenes. Mol. Pharmacol. 71: 1545-1553 [Abstract] [Full Text]  
  • Avallone, R., Demers, A., Rodrigue-Way, A., Bujold, K., Harb, D., Anghel, S., Wahli, W., Marleau, S., Ong, H., Tremblay, A. (2006). A Growth Hormone-Releasing Peptide that Binds Scavenger Receptor CD36 and Ghrelin Receptor Up-Regulates Sterol Transporters and Cholesterol Efflux in Macrophages through a Peroxisome Proliferator-Activated Receptor {gamma}-Dependent Pathway. Mol. Endocrinol. 20: 3165-3178 [Abstract] [Full Text]  
  • Yang, L., Chan, C.-C., Kwon, O.-S., Liu, S., McGhee, J., Stimpson, S. A., Chen, L. Z., Harrington, W. W., Symonds, W. T., Rockey, D. C. (2006). Regulation of peroxisome proliferator-activated receptor-{gamma} in liver fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G902-G911 [Abstract] [Full Text]  
  • Marathe, C., Bradley, M. N., Hong, C., Lopez, F., de Galarreta, C. M. R., Tontonoz, P., Castrillo, A. (2006). The Arginase II Gene Is an Anti-inflammatory Target of Liver X Receptor in Macrophages. J. Biol. Chem. 281: 32197-32206 [Abstract] [Full Text]  
  • Jiang, Y. J., Lu, B., Kim, P., Elias, P. M., Feingold, K. R. (2006). Regulation of ABCA1 expression in human keratinocytes and murine epidermis. J. Lipid Res. 47: 2248-2258 [Abstract] [Full Text]  
  • Quinet, E. M., Savio, D. A., Halpern, A. R., Chen, L., Schuster, G. U., Gustafsson, J.-A., Basso, M. D., Nambi, P. (2006). Liver X Receptor (LXR)-beta Regulation in LXR{alpha}-Deficient Mice: Implications for Therapeutic Targeting. Mol. Pharmacol. 70: 1340-1349 [Abstract] [Full Text]  
  • Hummasti, S., Tontonoz, P. (2006). The Peroxisome Proliferator-Activated Receptor N-Terminal Domain Controls Isotype-Selective Gene Expression and Adipogenesis. Mol. Endocrinol. 20: 1261-1275 [Abstract] [Full Text]  
  • Desvergne, B., Michalik, L., Wahli, W. (2006). Transcriptional Regulation of Metabolism. Physiol. Rev. 86: 465-514 [Abstract] [Full Text]  
  • Lee, C.-H., Plutzky, J. (2006). Liver X Receptor Activation and High-Density Lipoprotein Biology: A Reversal of Fortune?. Circulation 113: 5-8 [Full Text]  
  • Chen, M., Beaven, S., Tontonoz, P. (2005). Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha. J. Lipid Res. 46: 2570-2579 [Abstract] [Full Text]  
  • Cheema, S. K., Agarwal-Mawal, A., Murray, C. M., Tucker, S. (2005). Lack of stimulation of cholesteryl ester transfer protein by cholesterol in the presence of a high-fat diet. J. Lipid Res. 46: 2356-2366 [Abstract] [Full Text]  
  • Oram, J. F., Heinecke, J. W. (2005). ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease. Physiol. Rev. 85: 1343-1372 [Abstract] [Full Text]  
  • Lee, F. Y., Kast-Woelbern, H. R., Chang, J., Luo, G., Jones, S. A., Fishbein, M. C., Edwards, P. A. (2005). {alpha}-Crystallin Is a Target Gene of the Farnesoid X-activated Receptor in Human Livers. J. Biol. Chem. 280: 31792-31800 [Abstract] [Full Text]  
  • Soumian, S, Albrecht, C, Davies, A., Gibbs, R. (2005). ABCA1 and atherosclerosis. Vasc Med 10: 109-119 [Abstract]  
  • She, H., Xiong, S., Hazra, S., Tsukamoto, H. (2005). Adipogenic Transcriptional Regulation of Hepatic Stellate Cells. J. Biol. Chem. 280: 4959-4967 [Abstract] [Full Text]  
  • Davies, J. D., Carpenter, K. L. H., Challis, I. R., Figg, N. L., McNair, R., Proudfoot, D., Weissberg, P. L., Shanahan, C. M. (2005). Adipocytic Differentiation and Liver X Receptor Pathways Regulate the Accumulation of Triacylglycerols in Human Vascular Smooth Muscle Cells. J. Biol. Chem. 280: 3911-3919 [Abstract] [Full Text]  
  • Sheth, S. S., Castellani, L. W., Chari, S., Wagg, C., Thipphavong, C. K., Bodnar, J. S., Tontonoz, P., Attie, A. D., Lopaschuk, G. D., Lusis, A. J. (2005). Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition. J. Lipid Res. 46: 123-134 [Abstract] [Full Text]  
  • Blaschke, F., Leppanen, O., Takata, Y., Caglayan, E., Liu, J., Fishbein, M. C., Kappert, K., Nakayama, K. I., Collins, A. R., Fleck, E., Hsueh, W. A., Law, R. E., Bruemmer, D. (2004). Liver X Receptor Agonists Suppress Vascular Smooth Muscle Cell Proliferation and Inhibit Neointima Formation in Balloon-Injured Rat Carotid Arteries. Circ. Res. 95: e110-e123 [Abstract] [Full Text]  
  • Li, A. C., Glass, C. K. (2004). PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis. J. Lipid Res. 45: 2161-2173 [Abstract] [Full Text]  
  • Kawai, K., Sasaki, S., Morita, H., Ito, T., Suzuki, S., Misawa, H., Nakamura, H. (2004). Unliganded Thyroid Hormone Receptor-{beta}1 Represses Liver X Receptor {alpha}/Oxysterol-Dependent Transactivation. Endocrinology 145: 5515-5524 [Abstract] [Full Text]  
  • Anderson, S. P., Dunn, C., Laughter, A., Yoon, L., Swanson, C., Stulnig, T. M., Steffensen, K. R., Chandraratna, R. A.S., Gustafsson, J.-A., Corton, J. C. (2004). Overlapping Transcriptional Programs Regulated by the Nuclear Receptors Peroxisome Proliferator-Activated Receptor {alpha}, Retinoid X Receptor, and Liver X Receptor in Mouse Liver. Mol. Pharmacol. 66: 1440-1452 [Abstract] [Full Text]  
  • Wong, J., Quinn, C. M., Brown, A. J. (2004). Statins Inhibit Synthesis of an Oxysterol Ligand for the Liver X Receptor in Human Macrophages With Consequences for Cholesterol Flux. Arterioscler. Thromb. Vasc. Bio. 24: 2365-2371 [Abstract] [Full Text]  
  • Albrecht, C., Soumian, S., Amey, J.S., Sardini, A., Higgins, C.F., Davies, A.H., Gibbs, R.G.J. (2004). ABCA1 Expression in Carotid Atherosclerotic Plaques. Stroke 35: 2801-2806 [Abstract] [Full Text]  
  • Yue, L., Rasouli, N., Ranganathan, G., Kern, P. A., Mazzone, T. (2004). Divergent Effects of Peroxisome Proliferator-activated Receptor {gamma} Agonists and Tumor Necrosis Factor {alpha} on Adipocyte ApoE Expression. J. Biol. Chem. 279: 47626-47632 [Abstract] [Full Text]  
  • Ulven, S. M., Dalen, K. T., Gustafsson, J.-A., Nebb, H. I. (2004). Tissue-specific autoregulation of the LXR{alpha} gene facilitates induction of apoE in mouse adipose tissue. J. Lipid Res. 45: 2052-2062 [Abstract] [Full Text]  
  • Kino, T., Chrousos, G. P. (2004). Combating Atherosclerosis With LXR{alpha} And PPAR{alpha} Agonists: Is Rational Multitargeted Polypharmacy the Future of Therapeutics in Complex Diseases?. Mol. Interv. 4: 254-257 [Abstract] [Full Text]  
  • Quinet, E. M., Savio, D. A., Halpern, A. R., Chen, L., Miller, C. P., Nambi, P. (2004). Gene-selective modulation by a synthetic oxysterol ligand of the liver X receptor. J. Lipid Res. 45: 1929-1942 [Abstract] [Full Text]  
  • Szanto, A., Benko, S., Szatmari, I., Balint, B. L., Furtos, I., Ruhl, R., Molnar, S., Csiba, L., Garuti, R., Calandra, S., Larsson, H., Diczfalusy, U., Nagy, L. (2004). Transcriptional Regulation of Human CYP27 Integrates Retinoid, Peroxisome Proliferator-Activated Receptor, and Liver X Receptor Signaling in Macrophages. Mol. Cell. Biol. 24: 8154-8166 [Abstract] [Full Text]  
  • Hummasti, S., Laffitte, B. A., Watson, M. A., Galardi, C., Chao, L. C., Ramamurthy, L., Moore, J. T., Tontonoz, P. (2004). Liver X receptors are regulators of adipocyte gene expression but not differentiation: identification of apoD as a direct target. J. Lipid Res. 45: 616-625 [Abstract] [Full Text]  
  • Dalen, K. T., Ulven, S. M., Bamberg, K., Gustafsson, J.-A., Nebb, H. I. (2003). Expression of the Insulin-responsive Glucose Transporter GLUT4 in Adipocytes Is Dependent on Liver X Receptor {alpha}. J. Biol. Chem. 278: 48283-48291 [Abstract] [Full Text]  
  • Chisholm, J. W., Hong, J., Mills, S. A., Lawn, R. M. (2003). The LXR ligand T0901317 induces severe lipogenesis in the db/db diabetic mouse. J. Lipid Res. 44: 2039-2048 [Abstract] [Full Text]  
  • Lund, E. G., Menke, J. G., Sparrow, C. P. (2003). Liver X Receptor Agonists as Potential Therapeutic Agents for Dyslipidemia and Atherosclerosis. Arterioscler. Thromb. Vasc. Bio. 23: 1169-1177 [Abstract] [Full Text]  
  • Francis, G. A., Annicotte, J.-S., Auwerx, J. (2003). PPAR-{alpha} effects on the heart and other vascular tissues. Am. J. Physiol. Heart Circ. Physiol. 285: H1-H9 [Abstract] [Full Text]  
  • Tontonoz, P., Mangelsdorf, D. J. (2003). Liver X Receptor Signaling Pathways in Cardiovascular Disease. Mol. Endocrinol. 17: 985-993 [Abstract] [Full Text]  
  • Oram, J. F. (2003). HDL Apolipoproteins and ABCA1: Partners in the Removal of Excess Cellular Cholesterol. Arterioscler. Thromb. Vasc. Bio. 23: 720-727 [Abstract] [Full Text]  
  • Laffitte, B. A., Chao, L. C., Li, J., Walczak, R., Hummasti, S., Joseph, S. B., Castrillo, A., Wilpitz, D. C., Mangelsdorf, D. J., Collins, J. L., Saez, E., Tontonoz, P. (2003). Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc. Natl. Acad. Sci. USA 100: 5419-5424 [Abstract] [Full Text]  
  • Han, S.-R., Momeni, A., Strach, K., Suriyaphol, P., Fenske, D., Paprotka, K., Hashimoto, S. I., Torzewski, M., Bhakdi, S., Husmann, M. (2003). Enzymatically Modified LDL Induces Cathepsin H in Human Monocytes: Potential Relevance in Early Atherogenesis. Arterioscler. Thromb. Vasc. Bio. 23: 661-667 [Abstract] [Full Text]  
  • Castrillo, A., Joseph, S. B., Marathe, C., Mangelsdorf, D. J., Tontonoz, P. (2003). Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages. J. Biol. Chem. 278: 10443-10449 [Abstract] [Full Text]  
  • Juvet, L. K., Andresen, S. M., Schuster, G. U., Dalen, K. T., Tobin, K. A. R., Hollung, K., Haugen, F., Jacinto, S., Ulven, S. M., Bamberg, K., Gustafsson, J.-A., Nebb, H. I. (2003). On the Role of Liver X Receptors in Lipid Accumulation in Adipocytes. Mol. Endocrinol. 17: 172-182 [Abstract] [Full Text]  
  • Zhang, Y., Kast-Woelbern, H. R., Edwards, P. A. (2003). Natural Structural Variants of the Nuclear Receptor Farnesoid X Receptor Affect Transcriptional Activation. J. Biol. Chem. 278: 104-110 [Abstract] [Full Text]  
  • Stulnig, T. M., Steffensen, K. R., Gao, H., Reimers, M., Dahlman-Wright, K., Schuster, G. U., Gustafsson, J.-A. (2002). Novel Roles of Liver X Receptors Exposed by Gene Expression Profiling in Liver and Adipose Tissue. Mol. Pharmacol. 62: 1299-1305 [Abstract] [Full Text]  
  • Muscat, G. E. O., Wagner, B. L., Hou, J., Tangirala, R. K., Bischoff, E. D., Rohde, P., Petrowski, M., Li, J., Shao, G., Macondray, G., Schulman, I. G. (2002). Regulation of Cholesterol Homeostasis and Lipid Metabolism in Skeletal Muscle by Liver X Receptors. J. Biol. Chem. 277: 40722-40728 [Abstract] [Full Text]  
  • Wang, L., Schuster, G. U., Hultenby, K., Zhang, Q., Andersson, S., Gustafsson, J.-A. (2002). Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration. Proc. Natl. Acad. Sci. USA 99: 13878-13883 [Abstract] [Full Text]  
  • Brown, B. G., Cheung, M. C., Lee, A. C., Zhao, X.-Q., Chait, A. (2002). Antioxidant Vitamins and Lipid Therapy: End of a Long Romance?. Arterioscler. Thromb. Vasc. Bio. 22: 1535-1546 [Abstract] [Full Text]  
  • Chiang, J. Y. L. (2002). Bile Acid Regulation of Gene Expression: Roles of Nuclear Hormone Receptors. Endocr. Rev. 23: 443-463 [Abstract] [Full Text]  
  • Whitney, K. D., Watson, M. A., Collins, J. L., Benson, W. G., Stone, T. M., Numerick, M. J., Tippin, T. K., Wilson, J. G., Winegar, D. A., Kliewer, S. A. (2002). Regulation of Cholesterol Homeostasis by the Liver X Receptors in the Central Nervous System. Mol. Endocrinol. 16: 1378-1385 [Abstract] [Full Text]  
  • Joseph, S. B., McKilligin, E., Pei, L., Watson, M. A., Collins, A. R., Laffitte, B. A., Chen, M., Noh, G., Goodman, J., Hagger, G. N., Tran, J., Tippin, T. K., Wang, X., Lusis, A. J., Hsueh, W. A., Law, R. E., Collins, J. L., Willson, T. M., Tontonoz, P. (2002). Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc. Natl. Acad. Sci. USA 99: 7604-7609 [Abstract] [Full Text]  
  • Zhang, Y., Mangelsdorf, D. J. (2002). LuXuRies of Lipid Homeostasis: The Unity of Nuclear Hormone Receptors, Transcription Regulation, and Cholesterol Sensing. Mol. Interv. 2: 78-87 [Abstract] [Full Text]  
  • Walczak, R., Tontonoz, P. (2002). PPARadigms and PPARadoxes: expanding roles for PPAR{gamma} in the control of lipid metabolism. J. Lipid Res. 43: 177-186 [Abstract] [Full Text]  
  • Edwards, P. A., Kast, H. R., Anisfeld, A. M. (2002). BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis. J. Lipid Res. 43: 2-12 [Abstract] [Full Text]  
  • Whitney, K. D., Watson, M. A., Goodwin, B., Galardi, C. M., Maglich, J. M., Wilson, J. G., Willson, T. M., Collins, J. L., Kliewer, S. A. (2001). Liver X Receptor (LXR) Regulation of the LXRalpha Gene in Human Macrophages. J. Biol. Chem. 276: 43509-43515 [Abstract] [Full Text]  
  • Zaghini, I., Landrier, J.-F., Grober, J., Krief, S., Jones, S. A., Monnot, M.-C., Lefrere, I., Watson, M. A., Collins, J. L., Fujii, H., Besnard, P. (2002). Sterol Regulatory Element-binding Protein-1c Is Responsible for Cholesterol Regulation of Ileal Bile Acid-binding Protein Gene in Vivo. POSSIBLE INVOLVEMENT OF LIVER-X-RECEPTOR. J. Biol. Chem. 277: 1324-1331 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»