, 12:74 | Cite as

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

  • Shradha Wali
  • Rishein Gupta
  • Jieh-Juen Yu
  • Adelphe Mfuh
  • Xiaoli Gao
  • M. Neal Guentzel
  • James P. Chambers
  • Sazaly Abu Bakar
  • Guangming Zhong
  • Bernard P. ArulanandamEmail author
Original Article



Chlamydia trachomatis (Ct), is the leading cause of sexually transmitted infections worldwide. Host transcriptomic- or proteomic profiling studies have identified key molecules involved in establishment of Ct infection or the generation of anti Ct-immunity. However, the contribution of the host metabolome is not known.


The objective of this study was to determine the contribution of host metabolites in genital Ct infection.


We used high-performance liquid chromatography-mass spectrometry, and mapped lipid profiles in genital swabs obtained from female guinea pigs at days 3, 9, 15, 30 and 65 post Ct serovar D intravaginal infection.


Across all time points assessed, 13 distinct lipid species including choline, ethanolamine and glycerol were detected. Amongst these metabolites, phosphatidylcholine (PC) was the predominant phospholipid detected from animals actively shedding bacteria i.e., at 3, 9, and 15 days post infection. However, at days 30 and 65 when the animals had cleared the infection, PC was observed to be decreased compared to previous time points. Mass spectrometry analyses of PC produced in guinea pigs (in vivo) and 104C1 guinea pig cell line (in vitro) revealed distinct PC species following Ct D infection. Amongst these, PC 16:0/18:1 was significantly upregulated following Ct D infection (p < 0.05, >twofold change) in vivo and in vitro infection models investigated in this report. Exogenous addition of PC 16:0/18:1 resulted in significant increase in Ct D in Hela 229 cells.


This study demonstrates a role for host metabolite, PC 16:0/18:1 in regulating genital Ct infection in vivo and in vitro.


Guinea pig Chlamydia trachomatis serovar D Intravaginal infection Lipids Phosphatidylcholine 



We thank Dr. Roger Rank (Arkansas Children’s Hospital Research Institute) for sharing the 104C1 cell line, his support in establishing the guinea pig model and insightful discussions. We thank Drs. George R. Negrete and Oleg Larionov, Chemistry, UTSA for use of their equipment and reagents to prepare liposome encapsulated PC 16:0/18:1. This work was supported by National Institutes of Health (NIH) Grant (1RO3AI092621-01) and the Center for Excellence in Infection Genomics (CEIG) training Grant (DOD #W911NF-11-1-0136). Partial support of this study was from the Jane and Roland Blumberg Professorship in Biology for Dr. Arulanandam. Mass spectrometry analyses were conducted in the Metabolomics Core Facility of the Mass Spectrometry Laboratory at the University of Texas Health Science Center at San Antonio, with instrumentation funded in part by NIH Grant (1S10RR031586-01).

Compliance with ethical standards

Conflict of Interest

The authors have no conflicts of interest to declare in regards to this work.

Ethical approval

All Authors listed in this manuscript agree and comply with compliance with ethical requirements.

Supplementary material

11306_2016_998_MOESM1_ESM.tif (634 kb)
Fig. S1 PCA of Chlamydia trachomatis infected guinea pigs. Clusters obtained by principal component analysis (PCA) of log-scaled polar metabolite data of genital swabs obtained from Ct D and mock infected guinea pigs at days (a) 3, (b) 9 and (c) 15 post challenge. Supplementary material 1 (TIFF 634 kb)
11306_2016_998_MOESM2_ESM.docx (29 kb)
Table S1 Fold changes in representative species detected in various metabolite families following Chlamydia trachomatis D infection In vivo (swabs obtained from guinea pigs). Supplementary material 2 (DOCX 28 kb)


  1. Adekoya, N., Truman, B., Landen, M., & Centers for Disease, C., & Prevention. (2015). Incidence of notifiable diseases among American Indians/Alaska Natives—United States, 2007–2011. Morbidity and Mortality Weekly Report, 64(1), 16–19.PubMedGoogle Scholar
  2. Arkatkar, T., Gupta, R., Li, W., Yu, J. J., Wali, S., Neal Guentzel, M., et al. (2015). Murine MicroRNA-214 regulates intracellular adhesion molecule (ICAM1) gene expression in genital Chlamydia muridarum infection. Immunology, 145(4), 534–542. doi: 10.1111/imm.12470.CrossRefPubMedGoogle Scholar
  3. Banhart, S., Saied, E. M., Martini, A., Koch, S., Aeberhard, L., Madela, K., et al. (2014). Improved plaque assay identifies a novel anti-Chlamydia ceramide derivative with altered intracellular localization. Antimicrobial Agents and Chemotherapy, 58(9), 5537–5546. doi: 10.1128/AAC.03457-14.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Brotman, R. M., Ravel, J., Bavoil, P. M., Gravitt, P. E., & Ghanem, K. G. (2014). Microbiome, sex hormones, and immune responses in the reproductive tract: Challenges for vaccine development against sexually transmitted infections. Vaccine, 32(14), 1543–1552. doi: 10.1016/j.vaccine.2013.10.010.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Brunham, R. C., & Rappuoli, R. (2013). Chlamydia trachomatis control requires a vaccine. Vaccine, 31(15), 1892–1897. doi: 10.1016/j.vaccine.2013.01.024.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Capmany, A., & Damiani, M. T. (2010). Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication. PLoS ONE, 5(11), e14084. doi: 10.1371/journal.pone.0014084.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Carlson, J. H., Whitmire, W. M., Crane, D. D., Wicke, L., Virtaneva, K., Sturdevant, D. E., et al. (2008). The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor. Infection and Immunity, 76(6), 2273–2283. doi: 10.1128/IAI.00102-08.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Champion, C. I., Kickhoefer, V. A., Liu, G., Moniz, R. J., Freed, A. S., Bergmann, L. L., et al. (2009). A vault nanoparticle vaccine induces protective mucosal immunity. PLoS ONE, 4(4), e5409. doi: 10.1371/journal.pone.0005409.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cole, L. K., Dolinsky, V. W., Dyck, J. R., & Vance, D. E. (2011). Impaired phosphatidylcholine biosynthesis reduces atherosclerosis and prevents lipotoxic cardiac dysfunction in ApoE −/− Mice. Circulation Research, 108(6), 686–694. doi: 10.1161/CIRCRESAHA.110.238691.CrossRefPubMedGoogle Scholar
  10. Cole, L. K., Vance, J. E., & Vance, D. E. (2012). Phosphatidylcholine biosynthesis and lipoprotein metabolism. Biochimica et Biophysica Acta, 1821(5), 754–761. doi: 10.1016/j.bbalip.2011.09.009.CrossRefPubMedGoogle Scholar
  11. Cruz-Fisher, M. I., Cheng, C., Sun, G., Pal, S., Teng, A., Molina, D. M., et al. (2011). Identification of immunodominant antigens by probing a whole Chlamydia trachomatis open reading frame proteome microarray using sera from immunized mice. Infection and Immunity, 79(1), 246–257. doi: 10.1128/IAI.00626-10.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Cunningham, K., Stansfield, S. H., Patel, P., Menon, S., Kienzle, V., Allan, J. A., et al. (2013). The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection. BMC Immunol, 14, 50. doi: 10.1186/1471-2172-14-50.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Darville, T., & Hiltke, T. J. (2010). Pathogenesis of genital tract disease due to Chlamydia trachomatis. Journal of Infectious Diseases, 201(Suppl 2), S114–S125.CrossRefPubMedPubMedCentralGoogle Scholar
  14. de Alwis, N. M., & Day, C. P. (2008). Non-alcoholic fatty liver disease: The mist gradually clears. Journal of Hepatology, 48(Suppl 1), S104–S112. doi: 10.1016/j.jhep.2008.01.009.CrossRefPubMedGoogle Scholar
  15. De Clercq, E., Kalmar, I., & Vanrompay, D. (2013). Animal models for studying female genital tract infection with Chlamydia trachomatis. Infection and Immunity, 81(9), 3060–3067. doi: 10.1128/IAI.00357-13.CrossRefPubMedPubMedCentralGoogle Scholar
  16. de Jonge, M. I., Keizer, S. A., El Moussaoui, H. M., van Dorsten, L., Azzawi, R., van Zuilekom, H. I., et al. (2011). A novel guinea pig model of Chlamydia trachomatis genital tract infection. Vaccine, 29(35), 5994–6001. doi: 10.1016/j.vaccine.2011.06.037.CrossRefPubMedGoogle Scholar
  17. Derre, I. (2015). Chlamydiae interaction with the endoplasmic reticulum: Contact, function and consequences. Cellular Microbiology, 17(7), 959–966. doi: 10.1111/cmi.12455.CrossRefPubMedGoogle Scholar
  18. Derre, I., Swiss, R., & Agaisse, H. (2011). The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites. PLoS Pathogens, 7(6), e1002092. doi: 10.1371/journal.ppat.1002092.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Derrick, T., Roberts, C., Rajasekhar, M., Burr, S. E., Joof, H., Makalo, P., et al. (2013). Conjunctival MicroRNA expression in inflammatory trachomatous scarring. PLoS Neglected Tropical Diseases, 7(3), e2117. doi: 10.1371/journal.pntd.0002117.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Deruaz, M., & Luster, A. D. (2015). Chemokine-mediated immune responses in the female genital tract mucosa. Immunology and Cell Biology, 93(4), 347–354. doi: 10.1038/icb.2015.20.CrossRefPubMedGoogle Scholar
  21. Doria, M. L., Cotrim, Z., Macedo, B., Simoes, C., Domingues, P., Helguero, L., et al. (2012). Lipidomic approach to identify patterns in phospholipid profiles and define class differences in mammary epithelial and breast cancer cells. Breast Cancer Research and Treatment, 133(2), 635–648. doi: 10.1007/s10549-011-1823-5.CrossRefPubMedGoogle Scholar
  22. Elwell, C. A., & Engel, J. N. (2012). Lipid acquisition by intracellular Chlamydiae. Cellular Microbiology, 14(7), 1010–1018. doi: 10.1111/j.1462-5822.2012.01794.x.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Elwell, C. A., Jiang, S., Kim, J. H., Lee, A., Wittmann, T., Hanada, K., et al. (2011). Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathogens, 7(9), e1002198. doi: 10.1371/journal.ppat.1002198.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Fahy, E., Subramaniam, S., Murphy, R. C., Nishijima, M., Raetz, C. R., Shimizu, T., et al. (2009). Update of the LIPID MAPS comprehensive classification system for lipids. Journal of Lipid Research, 50(Suppl), S9–S14. doi: 10.1194/jlr.R800095-JLR200.PubMedPubMedCentralGoogle Scholar
  25. Ferreira, R., Borges, V., Nunes, A., Borrego, M. J., & Gomes, J. P. (2013). Assessment of the load and transcriptional dynamics of Chlamydia trachomatis plasmid according to strains’ tissue tropism. Microbiological Research, 168(6), 333–339. doi: 10.1016/j.micres.2013.02.001.CrossRefPubMedGoogle Scholar
  26. Furuse, Y., Finethy, R., Saka, H. A., Xet-Mull, A. M., Sisk, D. M., Smith, K. L., et al. (2014). Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells. PLoS ONE, 9(9), e106434. doi: 10.1371/journal.pone.0106434.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Gao, X., Zhang, Q., Meng, D., Isaac, G., Zhao, R., Fillmore, T. L., et al. (2012). A reversed-phase capillary ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for comprehensive top-down/bottom-up lipid profiling. Analytical and Bioanalytical Chemistry, 402(9), 2923–2933. doi: 10.1007/s00216-012-5773-5.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Gondek, D. C., Olive, A. J., Stary, G., & Starnbach, M. N. (2012). CD4 + T cells are necessary and sufficient to confer protection against Chlamydia trachomatis infection in the murine upper genital tract. J Immunol, 189(5), 2441–2449. doi: 10.4049/jimmunol.1103032.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Gottlieb, S. L., Low, N., Newman, L. M., Bolan, G., Kamb, M., & Broutet, N. (2014). Toward global prevention of sexually transmitted infections (STIs): The need for STI vaccines. Vaccine, 32(14), 1527–1535. doi: 10.1016/j.vaccine.2013.07.087.CrossRefPubMedGoogle Scholar
  30. Gross, R. W., & Han, X. (2011). Lipidomics at the interface of structure and function in systems biology. Chemistry & Biology, 18(3), 284–291. doi: 10.1016/j.chembiol.2011.01.014.CrossRefGoogle Scholar
  31. Gupta, R., Arkatkar, T., Yu, J. J., Wali, S., Haskins, W. E., Chambers, J. P., et al. (2015). Chlamydia muridarum infection associated host MicroRNAs in the murine genital tract and contribution to generation of host immune response. American Journal of Reproductive Immunology, 73(2), 126–140. doi: 10.1111/aji.12281.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hackstadt, T., Rockey, D. D., Heinzen, R. A., & Scidmore, M. A. (1996). Chlamydia trachomatis interrupts an exocytic pathway to acquire endogenously synthesized sphingomyelin in transit from the Golgi apparatus to the plasma membrane. EMBO Journal, 15(5), 964–977.PubMedPubMedCentralGoogle Scholar
  33. Hackstadt, T., Scidmore, M. A., & Rockey, D. D. (1995). Lipid metabolism in Chlamydia trachomatis-infected cells: Directed trafficking of Golgi-derived sphingolipids to the chlamydial inclusion. Proceedings of the National Academy of Sciences USA, 92(11), 4877–4881.CrossRefGoogle Scholar
  34. Hafner, L. M. (2015). Pathogenesis of fallopian tube damage caused by Chlamydia trachomatis infections. Contraception, 92(2), 108–115. doi: 10.1016/j.contraception.2015.01.004.CrossRefPubMedGoogle Scholar
  35. Hafner, L., Beagley, K., & Timms, P. (2008). Chlamydia trachomatis infection: Host immune responses and potential vaccines. Mucosal Immunology, 1(2), 116–130. doi: 10.1038/mi.2007.19.CrossRefPubMedGoogle Scholar
  36. Hafner, L. M., Wilson, D. P., & Timms, P. (2014). Development status and future prospects for a vaccine against Chlamydia trachomatis infection. Vaccine, 32(14), 1563–1571. doi: 10.1016/j.vaccine.2013.08.020.CrossRefPubMedGoogle Scholar
  37. Hatch, G. M., & McClarty, G. (2004). C. trachomatis-infection accelerates metabolism of phosphatidylcholine derived from low density lipoprotein but does not affect phosphatidylcholine secretion from hepatocytes. BMC Microbiology, 4, 8. doi: 10.1186/1471-2180-4-8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. He, Q., Takizawa, Y., Hayasaka, T., Masaki, N., Kusama, Y., Su, J., et al. (2014). Increased phosphatidylcholine (16:0/16:0) in the folliculus lymphaticus of Warthin tumor. Analytical and Bioanalytical Chemistry, 406(24), 5815–5825. doi: 10.1007/s00216-014-7890-9.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Huston, W. M., Harvie, M., Mittal, A., Timms, P., & Beagley, K. W. (2012). Vaccination to protect against infection of the female reproductive tract. Expert Review of Clinical Immunology, 8(1), 81–94. doi: 10.1586/eci.11.80.CrossRefPubMedGoogle Scholar
  40. Igietseme, J. U., Omosun, Y., Partin, J., Goldstein, J., He, Q., Joseph, K., et al. (2013). Prevention of Chlamydia-induced infertility by inhibition of local caspase activity. Journal of Infectious Diseases, 207(7), 1095–1104. doi: 10.1093/infdis/jit009.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Igietseme, J. U., Uriri, I. M., Kumar, S. N., Ananaba, G. A., Ojior, O. O., Momodu, I. A., et al. (1998). Route of infection that induces a high intensity of gamma interferon-secreting T cells in the genital tract produces optimal protection against Chlamydia trachomatis infection in mice. Infection and Immunity, 66(9), 4030–4035.PubMedPubMedCentralGoogle Scholar
  42. Ishikawa, S., Tateya, I., Hayasaka, T., Masaki, N., Takizawa, Y., Ohno, S., et al. (2012). Increased expression of phosphatidylcholine (16:0/18:1) and (16:0/18:2) in thyroid papillary cancer. PLoS ONE, 7(11), e48873. doi: 10.1371/journal.pone.0048873.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Jiang, J., Karimi, O., Ouburg, S., Champion, C. I., Khurana, A., Liu, G., et al. (2012). Interruption of CXCL13-CXCR5 axis increases upper genital tract pathology and activation of NKT cells following chlamydial genital infection. PLoS ONE, 7(11), e47487. doi: 10.1371/journal.pone.0047487.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Jupelli, M., Murthy, A. K., Chaganty, B. K., Guentzel, M. N., Selby, D. M., Vasquez, M. M., et al. (2011). Neonatal chlamydial pneumonia induces altered respiratory structure and function lasting into adult life. Laboratory Investigation, 91(10), 1530–1539. doi: 10.1038/labinvest.2011.103.CrossRefPubMedGoogle Scholar
  45. Karunakaran, K. P., Yu, H., Jiang, X., Chan, Q., Moon, K. M., Foster, L. J., et al. (2015). Outer membrane proteins preferentially load MHC class II peptides: Implications for a Chlamydia trachomatis T cell vaccine. Vaccine, 33(18), 2159–2166. doi: 10.1016/j.vaccine.2015.02.055.CrossRefPubMedGoogle Scholar
  46. Kokes, M., Dunn, J. D., Granek, J. A., Nguyen, B. D., Barker, J. R., Valdivia, R. H., et al. (2015). Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia. Cell Host & Microbe, 17(5), 716–725. doi: 10.1016/j.chom.2015.03.014.CrossRefGoogle Scholar
  47. Lal, J. A., Malogajski, J., Verweij, S. P., de Boer, P., Ambrosino, E., Brand, A., et al. (2013). Chlamydia trachomatis infections and subfertility: Opportunities to translate host pathogen genomic data into public health. Public Health Genomics, 16(1–2), 50–61. doi: 10.1159/000346207.CrossRefPubMedGoogle Scholar
  48. Li, S., Goins, B., Hrycushko, B. A., Phillips, W. T., & Bao, A. (2012a). Feasibility of eradication of breast cancer cells remaining in postlumpectomy cavity and draining lymph nodes following intracavitary injection of radioactive immunoliposomes. Molecular Pharmaceutics, 9(9), 2513–2522. doi: 10.1021/mp300132f.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Li, S., Goins, B., Zhang, L., & Bao, A. (2012b). Novel multifunctional theranostic liposome drug delivery system: Construction, characterization, and multimodality MR, near-infrared fluorescent, and nuclear imaging. Bioconjugate Chemistry, 23(6), 1322–1332. doi: 10.1021/bc300175d.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Li, W., Murthy, A. K., Guentzel, M. N., Seshu, J., Forsthuber, T. G., Zhong, G., et al. (2008). Antigen-specific CD4 + T cells produce sufficient IFN-gamma to mediate robust protective immunity against genital Chlamydia muridarum infection. Journal of Immunology, 180(5), 3375–3382.CrossRefGoogle Scholar
  51. Li, W., Murthy, A. K., Lanka, G. K., Chetty, S. L., Yu, J. J., Chambers, J. P., et al. (2013). A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4 transgenic mice. Vaccine, 31(48), 5722–5728. doi: 10.1016/j.vaccine.2013.09.036.CrossRefPubMedGoogle Scholar
  52. Lyons, J. M., Ouburg, S., & Morre, S. A. (2009). An integrated approach to Chlamydia trachomatis infection: The ICTI Consortium, an update. Drugs of Today, 45 Suppl B, 15–23.PubMedGoogle Scholar
  53. Mascellino, M. T., Boccia, P., & Oliva, A. (2011). Immunopathogenesis in Chlamydia trachomatis infected women. ISRN Obstetrics and Gynecol, 2011, 436936. doi: 10.5402/2011/436936.CrossRefGoogle Scholar
  54. Mfuh, A. M., Mahindaratne, M. P., Quintero, M. V., Lakner, F. J., Bao, A., Goins, B. A., et al. (2011). Novel asparagine-derived lipid enhances distearoylphosphatidylcholine bilayer resistance to acidic conditions. Langmuir, 27(8), 4447–4455. doi: 10.1021/la105085k.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Mirrashidi, K. M., Elwell, C. A., Verschueren, E., Johnson, J. R., Frando, A., Von Dollen, J., et al. (2015). Global mapping of the inc-human interactome reveals that retromer restricts chlamydia infection. Cell Host & Microbe, 18(1), 109–121. doi: 10.1016/j.chom.2015.06.004.CrossRefGoogle Scholar
  56. Moore, E. R., Fischer, E. R., Mead, D. J., & Hackstadt, T. (2008). The chlamydial inclusion preferentially intercepts basolaterally directed sphingomyelin-containing exocytic vacuoles. Traffic, 9(12), 2130–2140. doi: 10.1111/j.1600-0854.2008.00828.x.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Morrison, R. P., & Caldwell, H. D. (2002). Immunity to murine chlamydial genital infection. Infection and Immunity, 70(6), 2741–2751.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Muller, C., Dietz, I., Tziotis, D., Moritz, F., Rupp, J., & Schmitt-Kopplin, P. (2013). Molecular cartography in acute Chlamydia pneumoniae infections–a non-targeted metabolomics approach. Analytical and Bioanalytical Chemistry, 405(15), 5119–5131. doi: 10.1007/s00216-013-6732-5.CrossRefPubMedGoogle Scholar
  59. Murthy, A. K., Li, W., Chaganty, B. K., Kamalakaran, S., Guentzel, M. N., Seshu, J., et al. (2011). Tumor necrosis factor alpha production from CD8 + T cells mediates oviduct pathological sequelae following primary genital Chlamydia muridarum infection. Infection and Immunity, 79(7), 2928–2935. doi: 10.1128/IAI.05022-11.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Neuendorf, E., Gajer, P., Bowlin, A. K., Marques, P. X., Ma, B., Yang, H., et al. (2015). Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota. Pathogens and Disease, 73(4), ftv019. doi: 10.1093/femspd/ftv019.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Nogueira, C. V., Zhang, X., Giovannone, N., Sennott, E. L., & Starnbach, M. N. (2015). Protective immunity against Chlamydia trachomatis can engage both CD4 + and CD8 + T cells and bridge the respiratory and genital mucosae. Journal of Immunology, 194(5), 2319–2329. doi: 10.4049/jimmunol.1402675.CrossRefGoogle Scholar
  62. Oberley, R. E., Ault, K. A., Neff, T. L., Khubchandani, K. R., Crouch, E. C., & Snyder, J. M. (2004a). Surfactant proteins A and D enhance the phagocytosis of Chlamydia into THP-1 cells. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287(2), L296–L306. doi: 10.1152/ajplung.00440.2003.CrossRefPubMedGoogle Scholar
  63. Oberley, R. E., Goss, K. L., Ault, K. A., Crouch, E. C., & Snyder, J. M. (2004b). Surfactant protein D is present in the human female reproductive tract and inhibits Chlamydia trachomatis infection. Molecular Human Reproduction, 10(12), 861–870. doi: 10.1093/molehr/gah117.CrossRefPubMedGoogle Scholar
  64. Owusu-Edusei, K, Jr, Chesson, H. W., Gift, T. L., Brunham, R. C., & Bolan, G. (2015). Cost-effectiveness of Chlamydia vaccination programs for young women. Emerging Infectious Diseases, 21(6), 960–968. doi: 10.3201/eid2106.141270.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Owusu-Edusei, K, Jr, Chesson, H. W., Gift, T. L., Tao, G., Mahajan, R., Ocfemia, M. C., et al. (2013). The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sexually Transmitted Diseases, 40(3), 197–201. doi: 10.1097/OLQ.0b013e318285c6d2.CrossRefPubMedGoogle Scholar
  66. Ozolins, D., D’Elios, M. M., Lowndes, C. M., Unemo, M., & Members of the, N. C. S. C. (2013). Diagnostics, surveillance and management of sexually transmitted infections in Europe have to be improved: Lessons from the European Conference of National Strategies for Chlamydia trachomatis and Human papillomavirus (NSCP conference) in Latvia, 2011. Journal of the European Academy of Dermatology and Venereology, 27(10), 1308–1311. doi: 10.1111/j.1468-3083.2012.04545.x.PubMedGoogle Scholar
  67. Pan, Q., Pais, R., Ohandjo, A., He, C., He, Q., Omosun, Y., et al. (2015). Comparative evaluation of the protective efficacy of two formulations of a recombinant Chlamydia abortus subunit candidate vaccine in a mouse model. Vaccine, 33(15), 1865–1872. doi: 10.1016/j.vaccine.2015.02.007.CrossRefPubMedGoogle Scholar
  68. Perez-Gil, J. (2008). Structure of pulmonary surfactant membranes and films: The role of proteins and lipid-protein interactions. Biochimica et Biophysica Acta, 1778(7–8), 1676–1695. doi: 10.1016/j.bbamem.2008.05.003.CrossRefPubMedGoogle Scholar
  69. Picard, M. D., Cohane, K. P., Gierahn, T. M., Higgins, D. E., & Flechtner, J. B. (2012). High-throughput proteomic screening identifies Chlamydia trachomatis antigens that are capable of eliciting T cell and antibody responses that provide protection against vaginal challenge. Vaccine, 30(29), 4387–4393. doi: 10.1016/j.vaccine.2012.01.017.CrossRefPubMedGoogle Scholar
  70. Porcella, S. F., Carlson, J. H., Sturdevant, D. E., Sturdevant, G. L., Kanakabandi, K., Virtaneva, K., et al. (2015). Transcriptional profiling of human epithelial cells infected with plasmid-bearing and plasmid-deficient Chlamydia trachomatis. Infection and Immunity, 83(2), 534–543. doi: 10.1128/IAI.02764-14.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Qu, Y., Frazer, L. C., O’Connell, C. M., Tarantal, A. F., Andrews, C. W, Jr, O’Connor, S. L., et al. (2015). Comparable genital tract infection, pathology, and immunity in rhesus macaques inoculated with wild-type or plasmid-deficient Chlamydia trachomatis serovar D. Infection and Immunity,. doi: 10.1128/IAI.00841-15.PubMedGoogle Scholar
  72. Rank, R. G., Bowlin, A. K., Reed, R. L., & Darville, T. (2003). Characterization of chlamydial genital infection resulting from sexual transmission from male to female guinea pigs and determination of infectious dose. Infection and Immunity, 71(11), 6148–6154.CrossRefPubMedPubMedCentralGoogle Scholar
  73. Rank, R. G., & Whittum-Hudson, J. A. (2010). Protective immunity to chlamydial genital infection: Evidence from animal studies. Journal of Infectious Diseases, 201(Suppl 2), S168–S177. doi: 10.1086/652399.CrossRefPubMedGoogle Scholar
  74. Rey-Ladino, J., Ross, A. G., & Cripps, A. W. (2014). Immunity, immunopathology, and human vaccine development against sexually transmitted Chlamydia trachomatis. Human Vaccines & Immunotherapeutics, 10(9), 2664–2673. doi: 10.4161/hv.29683.CrossRefGoogle Scholar
  75. Saka, H. A., Thompson, J. W., Chen, Y. S., Dubois, L. G., Haas, J. T., Moseley, A., et al. (2015). Chlamydia trachomatis infection leads to defined alterations to the lipid droplet proteome in epithelial cells. PLoS ONE, 10(4), e0124630. doi: 10.1371/journal.pone.0124630.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Sanadgol, N., Mostafaie, A., Mansouri, K., & Bahrami, G. (2012). Effect of palmitic acid and linoleic acid on expression of ICAM-1 and VCAM-1 in human bone marrow endothelial cells (HBMECs). Arch Med Sci, 8(2), 192–198. doi: 10.5114/aoms.2012.28544.CrossRefPubMedPubMedCentralGoogle Scholar
  77. Shimomura, H., Hosoda, K., Hayashi, S., Yokota, K., Oguma, K., & Hirai, Y. (2009). Steroids mediate resistance to the bactericidal effect of phosphatidylcholines against Helicobacter pylori. FEMS Microbiology Letters, 301(1), 84–94. doi: 10.1111/j.1574-6968.2009.01807.x.CrossRefPubMedGoogle Scholar
  78. Sixt, B. S., Siegl, A., Muller, C., Watzka, M., Wultsch, A., Tziotis, D., et al. (2013). Metabolic features of Protochlamydia amoebophila elementary bodies—A link between activity and infectivity in Chlamydiae. PLoS Pathogens, 9(8), e1003553. doi: 10.1371/journal.ppat.1003553.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Stubbs, C. D., & Smith, A. D. (1984). The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochimica et Biophysica Acta, 779(1), 89–137.CrossRefPubMedGoogle Scholar
  80. Subramaniam, S., Fahy, E., Gupta, S., Sud, M., Byrnes, R. W., Cotter, D., et al. (2011). Bioinformatics and systems biology of the lipidome. Chemical Reviews, 111(10), 6452–6490. doi: 10.1021/cr200295k.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Szaszak, M., Chang, J. C., Leng, W., Rupp, J., Ojcius, D. M., & Kelley, A. M. (2013). Characterizing the intracellular distribution of metabolites in intact Chlamydia-infected cells by Raman and two-photon microscopy. Microbes and Infection, 15(6–7), 461–469. doi: 10.1016/j.micinf.2013.03.005.CrossRefPubMedPubMedCentralGoogle Scholar
  82. Torrone, E., Papp, J., Weinstock, H., & Centers for Disease, C., & Prevention. (2014). Prevalence of Chlamydia trachomatis genital infection among persons aged 14–39 years—United States, 2007–2012. Morbidity and Mortality Weekly Report, 63(38), 834–838.PubMedGoogle Scholar
  83. Uhl, O., Demmelmair, H., Segura, M. T., Florido, J., Rueda, R., Campoy, C., et al. (2015). Effects of obesity and gestational diabetes mellitus on placental phospholipids. Diabetes Research and Clinical Practice, 109(2), 364–371. doi: 10.1016/j.diabres.2015.05.032.CrossRefPubMedGoogle Scholar
  84. van Ooij, C., Kalman, L., van Ijzendoorn, S., Nishijima, M., Hanada, K., Mostov, K., et al. (2000). Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis. Cellular Microbiology, 2(6), 627–637.CrossRefPubMedGoogle Scholar
  85. Vanrompay, D., Hoang, T. Q., De Vos, L., Verminnen, K., Harkinezhad, T., Chiers, K., et al. (2005). Specific-pathogen-free pigs as an animal model for studying Chlamydia trachomatis genital infection. Infection and Immunity, 73(12), 8317–8321. doi: 10.1128/IAI.73.12.8317-8321.2005.CrossRefPubMedPubMedCentralGoogle Scholar
  86. Vasilevsky, S., Greub, G., Nardelli-Haefliger, D., & Baud, D. (2014). Genital Chlamydia trachomatis: Understanding the roles of innate and adaptive immunity in vaccine research. Clinical Microbiology Reviews, 27(2), 346–370. doi: 10.1128/CMR.00105-13.CrossRefPubMedPubMedCentralGoogle Scholar
  87. Wali, S., Gupta, R., Veselenak, R. L., Li, Y., Yu, J. J., Murthy, A. K., et al. (2014). Use of a Guinea pig-specific transcriptome array for evaluation of protective immunity against genital chlamydial infection following intranasal vaccination in Guinea pigs. PLoS ONE, 9(12), e114261. doi: 10.1371/journal.pone.0114261.CrossRefPubMedPubMedCentralGoogle Scholar
  88. Wang, J., Zhang, Y., Lu, C., Lei, L., Yu, P., & Zhong, G. (2010). A genome-wide profiling of the humoral immune response to Chlamydia trachomatis infection reveals vaccine candidate antigens expressed in humans. Journal of Immunology, 185(3), 1670–1680. doi: 10.4049/jimmunol.1001240.CrossRefGoogle Scholar
  89. Wylie, J. L., Hatch, G. M., & McClarty, G. (1997). Host cell phospholipids are trafficked to and then modified by Chlamydia trachomatis. Journal of Bacteriology, 179(23), 7233–7242.PubMedPubMedCentralGoogle Scholar
  90. Yeruva, L., Myers, G. S., Spencer, N., Creasy, H. H., Adams, N. E., Maurelli, A. T., et al. (2014). Early microRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection. MBio, 5(3), e01241-14. doi: 10.1128/mBio.01241-14.CrossRefPubMedPubMedCentralGoogle Scholar
  91. Zhou, B. R., Zhang, J. A., Zhang, Q., Permatasari, F., Xu, Y., Wu, D., et al. (2013). Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha via a NF-kappaB-dependent mechanism in HaCaT keratinocytes. Mediators of Inflammation, 2013, 530429. doi: 10.1155/2013/530429.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shradha Wali
    • 1
  • Rishein Gupta
    • 1
  • Jieh-Juen Yu
    • 1
  • Adelphe Mfuh
    • 2
  • Xiaoli Gao
    • 3
  • M. Neal Guentzel
    • 1
  • James P. Chambers
    • 1
  • Sazaly Abu Bakar
    • 4
  • Guangming Zhong
    • 5
  • Bernard P. Arulanandam
    • 1
    Email author
  1. 1.South Texas Center for Emerging Infectious Diseases and Center for Excellence in Infection GenomicsUniversity of Texas at San AntonioSan AntonioUSA
  2. 2.Department of ChemistryUniversity of Texas at San AntonioSan AntonioUSA
  3. 3.Department of BiochemistryUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  4. 4.Department of Medical Microbiology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  5. 5.Department of Microbiology and ImmunologyUniversity of Texas Health Science Center at San AntonioSan AntonioUSA

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