Guinea Pig Genital Tract Lipidome Reveals in Vivo and in Vitro Regulation of Phosphatidylcholine 16:0/18:1 and Contribution to Serovar D Infectivity

Overview

Journal Metabolomics

Publisher Springer

Specialty Endocrinology

Date 2016 Sep 20

PMID 27642272

Citations 2

Authors

Shradha Wali

Rishein Gupta

Jieh-Juen Yu

Adelphe Mfuh

Xiaoli Gao

M Neal Guentzel

James P Chambers

Sazaly Abu Bakar

Guangming Zhong

Bernard P Arulanandam

Affiliations

Soon will be listed here.

Abstract

Introduction: (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 ( < 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.

Citing Articles

Lipid profiles and differential lipids in serum related to severity of community-acquired pneumonia: A pilot study.

Chen L, Zheng Y, Zhao L, Zhang Y, Yin L, He Y PLoS One. 2021; 16(3):e0245770.

PMID: 33705428 PMC: 7951898. DOI: 10.1371/journal.pone.0245770.

Lipidomic profiling of amniotic fluid and its application in fetal lung maturity prediction.

Cao Z, Liu J, Xie X, Zhan S, Song W, Wu S J Clin Lab Anal. 2019; 34(4):e23109.

PMID: 31804000 PMC: 7171342. DOI: 10.1002/jcla.23109.

References

Mfuh A, Mahindaratne M, Quintero M, Lakner F, Bao A, Goins B . Novel asparagine-derived lipid enhances distearoylphosphatidylcholine bilayer resistance to acidic conditions. Langmuir. 2011; 27(8):4447-55. PMC: 3539164. DOI: 10.1021/la105085k. View

Kokes M, Dunn J, Granek J, Nguyen B, Barker J, Valdivia R . Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia. Cell Host Microbe. 2015; 17(5):716-25. PMC: 4418230. DOI: 10.1016/j.chom.2015.03.014. View

Owusu-Edusei Jr K, Chesson H, Gift T, Tao G, Mahajan R, Ocfemia M . The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sex Transm Dis. 2013; 40(3):197-201. DOI: 10.1097/OLQ.0b013e318285c6d2. View

Hafner L . Pathogenesis of fallopian tube damage caused by Chlamydia trachomatis infections. Contraception. 2015; 92(2):108-15. DOI: 10.1016/j.contraception.2015.01.004. View

Hafner L, Wilson D, Timms P . Development status and future prospects for a vaccine against Chlamydia trachomatis infection. Vaccine. 2013; 32(14):1563-71. DOI: 10.1016/j.vaccine.2013.08.020. View

Saka H, Thompson J, Chen Y, Dubois L, Haas J, Moseley A . Chlamydia trachomatis Infection Leads to Defined Alterations to the Lipid Droplet Proteome in Epithelial Cells. PLoS One. 2015; 10(4):e0124630. PMC: 4409204. DOI: 10.1371/journal.pone.0124630. View

Sixt B, Siegl A, Muller C, Watzka M, Wultsch A, Tziotis D . Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae. PLoS Pathog. 2013; 9(8):e1003553. PMC: 3738481. DOI: 10.1371/journal.ppat.1003553. View

Cruz-Fisher M, Cheng C, Sun G, Pal S, Teng A, Molina D . Identification of immunodominant antigens by probing a whole Chlamydia trachomatis open reading frame proteome microarray using sera from immunized mice. Infect Immun. 2010; 79(1):246-57. PMC: 3019893. DOI: 10.1128/IAI.00626-10. View

Qu Y, Frazer L, OConnell C, Tarantal A, Andrews Jr C, OConnor S . Comparable Genital Tract Infection, Pathology, and Immunity in Rhesus Macaques Inoculated with Wild-Type or Plasmid-Deficient Chlamydia trachomatis Serovar D. Infect Immun. 2015; 83(10):4056-67. PMC: 4567646. DOI: 10.1128/IAI.00841-15. View

10.

Neuendorf E, Gajer P, Bowlin A, Marques P, Ma B, Yang H . Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota. Pathog Dis. 2015; 73(4). PMC: 4445005. DOI: 10.1093/femspd/ftv019. View

11.

Gottlieb S, Low N, Newman L, Bolan G, Kamb M, Broutet N . Toward global prevention of sexually transmitted infections (STIs): the need for STI vaccines. Vaccine. 2014; 32(14):1527-35. PMC: 6794147. DOI: 10.1016/j.vaccine.2013.07.087. View

12.

Capmany A, Damiani M . Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication. PLoS One. 2010; 5(11):e14084. PMC: 2989924. DOI: 10.1371/journal.pone.0014084. View

13.

Uhl O, Demmelmair H, Segura M, Florido J, Rueda R, Campoy C . Effects of obesity and gestational diabetes mellitus on placental phospholipids. Diabetes Res Clin Pract. 2015; 109(2):364-71. DOI: 10.1016/j.diabres.2015.05.032. View

14.

Picard M, Cohane K, Gierahn T, Higgins D, Flechtner J . 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. 2012; 30(29):4387-93. DOI: 10.1016/j.vaccine.2012.01.017. View

15.

Wang J, Zhang Y, Lu C, Lei L, Yu P, Zhong G . A genome-wide profiling of the humoral immune response to Chlamydia trachomatis infection reveals vaccine candidate antigens expressed in humans. J Immunol. 2010; 185(3):1670-80. DOI: 10.4049/jimmunol.1001240. View

16.

Hatch G, McClarty G . C. trachomatis-infection accelerates metabolism of phosphatidylcholine derived from low density lipoprotein but does not affect phosphatidylcholine secretion from hepatocytes. BMC Microbiol. 2004; 4:8. PMC: 362871. DOI: 10.1186/1471-2180-4-8. View

17.

Carlson J, Whitmire W, Crane D, Wicke L, Virtaneva K, Sturdevant D . The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal genes and a virulence factor. Infect Immun. 2008; 76(6):2273-83. PMC: 2423098. DOI: 10.1128/IAI.00102-08. View

18.

Sanadgol N, Mostafaie A, Mansouri K, Bahrami G . 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. 2012; 8(2):192-8. PMC: 3361029. DOI: 10.5114/aoms.2012.28544. View

19.

Cole L, Dolinsky V, Dyck J, Vance D . Impaired phosphatidylcholine biosynthesis reduces atherosclerosis and prevents lipotoxic cardiac dysfunction in ApoE-/- Mice. Circ Res. 2011; 108(6):686-94. DOI: 10.1161/CIRCRESAHA.110.238691. View

20.

Derrick T, Roberts C, Rajasekhar M, Burr S, Joof H, Makalo P . Conjunctival MicroRNA expression in inflammatory trachomatous scarring. PLoS Negl Trop Dis. 2013; 7(3):e2117. PMC: 3597489. DOI: 10.1371/journal.pntd.0002117. View