Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Introduction

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.

Objectives

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

Methods

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.

Results

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.

Conclusion

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

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Darville, T., & Hiltke, T. J. (2010). Pathogenesis of genital tract disease due to Chlamydia trachomatis. Journal of Infectious Diseases, 201(Suppl 2), S114–S125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Derre, I. (2015). Chlamydiae interaction with the endoplasmic reticulum: Contact, function and consequences. Cellular Microbiology, 17(7), 959–966. doi:10.1111/cmi.12455.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrison, R. P., & Caldwell, H. D. (2002). Immunity to murine chlamydial genital infection. Infection and Immunity, 70(6), 2741–2751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

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).

Author information

Author notes

    Authors and Affiliations

    1. South Texas Center for Emerging Infectious Diseases and Center for Excellence in Infection Genomics, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249, USA

      Shradha Wali, Rishein Gupta, Jieh-Juen Yu, M. Neal Guentzel, James P. Chambers & Bernard P. Arulanandam

    2. Department of Chemistry, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249, USA

      Adelphe Mfuh

    3. Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

      Xiaoli Gao

    4. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai Kuala Lumpur, 50603, Kuala Lumpur, Malaysia

      Sazaly Abu Bakar

    5. Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7702 Floyd Curl Drive, San Antonio, TX, 78229, USA

      Guangming Zhong

    Authors
    1. Shradha Wali
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Rishein Gupta
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Jieh-Juen Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Adelphe Mfuh
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiaoli Gao
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. M. Neal Guentzel
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. James P. Chambers
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Sazaly Abu Bakar
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Guangming Zhong
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Bernard P. Arulanandam
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Bernard P. Arulanandam.

    Ethics declarations

    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.

    Additional information

    Shradha Wali and Rishein Gupta have contributed equally.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    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)

    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)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Wali, S., Gupta, R., Yu, JJ. et al. 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. Metabolomics 12, 74 (2016). https://doi.org/10.1007/s11306-016-0998-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • DOI: https://doi.org/10.1007/s11306-016-0998-5

    Keywords

    Search

    Navigation