Shradha Wali1, Rishein Gupta1, Jieh-Juen Yu1, Adelphe Mfuh2, Xiaoli Gao3, M Neal Guentzel1, James P Chambers1, Sazaly Abu Bakar4, Guangming Zhong5, Bernard P Arulanandam1. 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. 2. Department of Chemistry, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA. 3. Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. 4. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai Kuala Lumpur, 50603 Kuala Lumpur, Malaysia. 5. Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7702 Floyd Curl Drive, San Antonio, TX 78229, USA.
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.
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 Ctinfection 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 Ctinfection. 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 Ctinfection in vivo and in vitro.
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