A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo
Chlamydia is the most frequently reported sexually transmitted bacteria causing 2.9 million infections annually in the United States. Diagnosis, treatment, and sequelae of chlamydial disease cost billions of dollars each year in the United States alone. Considering that a heparin sulfate-like cell s...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-01-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.03269/full |
| _version_ | 1830484638009655296 |
|---|---|
| author | Karen M. Gallegos Christopher R. Taylor Christopher R. Taylor Daniel J. Rabulinski Rosalinda Del Toro Danielle E. Girgis Dapinder Jourha Vaibhav Tiwari Umesh R. Desai Kyle H. Ramsey |
| author_facet | Karen M. Gallegos Christopher R. Taylor Christopher R. Taylor Daniel J. Rabulinski Rosalinda Del Toro Danielle E. Girgis Dapinder Jourha Vaibhav Tiwari Umesh R. Desai Kyle H. Ramsey |
| author_sort | Karen M. Gallegos |
| collection | DOAJ |
| description | Chlamydia is the most frequently reported sexually transmitted bacteria causing 2.9 million infections annually in the United States. Diagnosis, treatment, and sequelae of chlamydial disease cost billions of dollars each year in the United States alone. Considering that a heparin sulfate-like cell surface receptor is involved in Chlamydia infections, we reasoned that sulfated and sulfonated mimics of heparin sulfate would be useful in topical prophylactic prevention of Chlamydia. In this study, we tested a small, synthetic sulfated agent sulfated pentagalloyl glucoside (SPGG) and three synthetic sulfonated polymers PSS and SPS with average molecular weight in the range of 11 to 1000 kDa for inhibition against Chlamydia. Infection of HeLa cells with C. muridarum or C. trachomatis in the presence of increasing concentrations of SPGG or sulfonated polymers were quantified by immunofluorescence of Chlamydia inclusions. To determine whether in vitro pre-treatment of SPGG inhibits infection of C. muridarum, HeLa monolayers were incubated with SPGG-containing media, and then infected with Chlamydia. Our in vitro results show that SPGG pre-treatment inhibits Chlamydia infection in a dose-dependent manner. In addition, we further determined if SPGG treatment has an inhibitory effect during infection, therefore cell monolayers were infected with C. muridarum in the concurrent presence of SPGG. Our results show that SPGG inhibits C. muridarum infection with an IC50 at 10 μg/ml levels. We also tested the inhibitory effect of synthetic polymers PSS and SPS against Chlamydia and found inhibition of C. muridarum and C. trachomatis infections with IC50 ranging from 0.3 to 0.8 μg/ml. SPGG, PSS, and SPS inhibit formation of Chlamydia inclusions in a concentration-dependent manner. For evaluation of in vivo efficacy of the most effective agent in blocking C. muridarum, SPGG, we intravaginally pre-treated mice with SPGG before infection with C. muridarum. Cervical swabs were collected post-infection to quantify Chlamydia inclusions in vitro. Our in vivo data show that the SPGG-treated group has a statistically significant reduction of infection compared to the no-treatment control. Overall, our results show that SPGG could serve as a promising topical inhibitor for preventing Chlamydia infection. |
| first_indexed | 2024-12-21T18:11:55Z |
| format | Article |
| id | doaj.art-7feffff1aaf94447bd09703d724f7773 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T18:11:55Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7feffff1aaf94447bd09703d724f77732022-12-21T18:54:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-01-01910.3389/fmicb.2018.03269427424A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivoKaren M. Gallegos0Christopher R. Taylor1Christopher R. Taylor2Daniel J. Rabulinski3Rosalinda Del Toro4Danielle E. Girgis5Dapinder Jourha6Vaibhav Tiwari7Umesh R. Desai8Kyle H. Ramsey9Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesDepartment of Dermatology, Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado – Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesInstitute for Structural Biology, Drug Discovery and Development, Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL, United StatesChlamydia is the most frequently reported sexually transmitted bacteria causing 2.9 million infections annually in the United States. Diagnosis, treatment, and sequelae of chlamydial disease cost billions of dollars each year in the United States alone. Considering that a heparin sulfate-like cell surface receptor is involved in Chlamydia infections, we reasoned that sulfated and sulfonated mimics of heparin sulfate would be useful in topical prophylactic prevention of Chlamydia. In this study, we tested a small, synthetic sulfated agent sulfated pentagalloyl glucoside (SPGG) and three synthetic sulfonated polymers PSS and SPS with average molecular weight in the range of 11 to 1000 kDa for inhibition against Chlamydia. Infection of HeLa cells with C. muridarum or C. trachomatis in the presence of increasing concentrations of SPGG or sulfonated polymers were quantified by immunofluorescence of Chlamydia inclusions. To determine whether in vitro pre-treatment of SPGG inhibits infection of C. muridarum, HeLa monolayers were incubated with SPGG-containing media, and then infected with Chlamydia. Our in vitro results show that SPGG pre-treatment inhibits Chlamydia infection in a dose-dependent manner. In addition, we further determined if SPGG treatment has an inhibitory effect during infection, therefore cell monolayers were infected with C. muridarum in the concurrent presence of SPGG. Our results show that SPGG inhibits C. muridarum infection with an IC50 at 10 μg/ml levels. We also tested the inhibitory effect of synthetic polymers PSS and SPS against Chlamydia and found inhibition of C. muridarum and C. trachomatis infections with IC50 ranging from 0.3 to 0.8 μg/ml. SPGG, PSS, and SPS inhibit formation of Chlamydia inclusions in a concentration-dependent manner. For evaluation of in vivo efficacy of the most effective agent in blocking C. muridarum, SPGG, we intravaginally pre-treated mice with SPGG before infection with C. muridarum. Cervical swabs were collected post-infection to quantify Chlamydia inclusions in vitro. Our in vivo data show that the SPGG-treated group has a statistically significant reduction of infection compared to the no-treatment control. Overall, our results show that SPGG could serve as a promising topical inhibitor for preventing Chlamydia infection.https://www.frontiersin.org/article/10.3389/fmicb.2018.03269/fullChlamydia trachomatisChlamydia muridaruminhibitionglucosideSPGG |
| spellingShingle | Karen M. Gallegos Christopher R. Taylor Christopher R. Taylor Daniel J. Rabulinski Rosalinda Del Toro Danielle E. Girgis Dapinder Jourha Vaibhav Tiwari Umesh R. Desai Kyle H. Ramsey A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo Frontiers in Microbiology Chlamydia trachomatis Chlamydia muridarum inhibition glucoside SPGG |
| title | A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo |
| title_full | A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo |
| title_fullStr | A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo |
| title_full_unstemmed | A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo |
| title_short | A Synthetic, Small, Sulfated Agent Is a Promising Inhibitor of Chlamydia spp. Infection in vivo |
| title_sort | synthetic small sulfated agent is a promising inhibitor of chlamydia spp infection in vivo |
| topic | Chlamydia trachomatis Chlamydia muridarum inhibition glucoside SPGG |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.03269/full |
| work_keys_str_mv | AT karenmgallegos asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT christopherrtaylor asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT christopherrtaylor asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT danieljrabulinski asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT rosalindadeltoro asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT danielleegirgis asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT dapinderjourha asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT vaibhavtiwari asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT umeshrdesai asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT kylehramsey asyntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT karenmgallegos syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT christopherrtaylor syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT christopherrtaylor syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT danieljrabulinski syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT rosalindadeltoro syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT danielleegirgis syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT dapinderjourha syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT vaibhavtiwari syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT umeshrdesai syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo AT kylehramsey syntheticsmallsulfatedagentisapromisinginhibitorofchlamydiasppinfectioninvivo |