Pelvic inflammatory disease (PID) is caused by both sexually transmitted pathogens, including Neiserria gonorrhoeae and Chlamydia trachomatis, and anaerobic and facultative pathogens.The broad, long term goal of this project is to use both culture-based methods and nucleic acid-based technology to characterize the microorganisms recovered from the endometrial tissues of women with suspected pelvic inflammatory disease (PlD).These data will provide novel data on the etiology of PID and will inform appropriate antimicrobic therapy for PID. Our preliminary data suggests that many of the microorganisms recovered from the endometrial biopsy samples of women with suspected PID using culture methodology in our laboratory do not fit any known taxonomic group based on phenotypic characteristics. Specifically, we propose to: 1) describe the microorganisms in 700 endometrial tissue samples obtained from 250 women enrolled in the acute PID cohort and 200 women enrolled in the cervicitis cohort (Core B), 2) apply genetic sequencing methodology to characterize the novel organisms recovered from the endometrial samples in order to place these organisms into taxonomic groups and to assess whether some organisms are more strongly associated with histologic evidence of endometritis and the signs and symptoms of acute PID, 3) perform antimicrobic susceptibility testing of all organisms recovered from the endometrial samples in order to assess current antibiotic treatments for women with acute PID are appropriate, 4) assess the presence of novel endometrial pathogens in the lower reproductive tract using vaginal samples obtained from women at enrollment through specific nucleic acid probes developed from nucleic acid of unique organisms recovered from the endometrial samples and 5) perform full genomic sequencing of some of the novel bacteria recovered from women with acute PID and/or histologic evidence of acute endometritis in order to establish the identity and correct taxonomic placement of these organisms. At the conclusion of the proposed studies, the role and identity of novel organisms associated with PID will be identified and may form the basis for improved treatment strategies. This project will be supported by Core B, Project 1 and Project 4.

Public Health Relevance

Pelvic inflammatory disease (PID) causes infertility and chronic pelvic pain in women woridwide. This project will identify previously underscribed organisms causing PID and will inform improved treatments.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-MMT-M)
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University of Pittsburgh
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Zheng, Xiaojing; O'Connell, Catherine M; Zhong, Wujuan et al. (2018) Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women. Front Cell Infect Microbiol 8:307
Zheng, Xiaojing; O'Connell, Catherine M; Zhong, Wujuan et al. (2018) Discovery of Blood Transcriptional Endotypes in Women with Pelvic Inflammatory Disease. J Immunol 200:2941-2956
Rahman, K Shamsur; Darville, Toni; Wiesenfeld, Harold C et al. (2018) Mixed Chlamydia trachomatis Peptide Antigens Provide a Specific and Sensitive Single-Well Colorimetric Enzyme-Linked Immunosorbent Assay for Detection of Human Anti-C. trachomatis Antibodies. mSphere 3:
Taylor, Brandie D; Zheng, Xiaojing; O'Connell, Catherine M et al. (2018) Risk factors for Mycoplasma genitalium endometritis and incident infection: a secondary data analysis of the T cell Response Against Chlamydia (TRAC) Study. Sex Transm Infect 94:414-420
Rahman, K Shamsur; Darville, Toni; Russell, Ali N et al. (2018) Comprehensive Molecular Serology of Human Chlamydia trachomatis Infections by Peptide Enzyme-Linked Immunosorbent Assays. mSphere 3:
Rahman, K Shamsur; Darville, Toni; Russell, Ali N et al. (2018) Discovery of Human-Specific Immunodominant Chlamydia trachomatis B Cell Epitopes. mSphere 3:
Taylor, Brandie D; Zheng, Xiaojing; Darville, Toni et al. (2017) Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease. Sex Transm Dis 44:35-41
Poston, Taylor B; Qu, Yanyan; Girardi, Jenna et al. (2017) A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function. J Immunol 199:2845-2854
Petrina, Melinda A B; Cosentino, Lisa A; Rabe, Lorna K et al. (2017) Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin. Anaerobe 47:115-119
Russell, Ali N; Zheng, Xiaojing; O'Connell, Catherine M et al. (2016) Identification of Chlamydia trachomatis Antigens Recognized by T Cells From Highly Exposed Women Who Limit or Resist Genital Tract Infection. J Infect Dis 214:1884-1892

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