The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i>
New therapeutic agents for cryptosporidiosis are a critical medical need. The marine organic compound, tartrolon E (trtE), is highly effective against multiple apicomplexan parasites, including <i>Cryptosporidium</i>. Understanding the mechanism of action of trtE is required to advance i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/11/2260 |
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| author | Alexis Cotto-Rosario Emma Y. D. Miller Fernanda G. Fumuso Jason A. Clement Matthew J. Todd Roberta M. O’Connor |
| author_facet | Alexis Cotto-Rosario Emma Y. D. Miller Fernanda G. Fumuso Jason A. Clement Matthew J. Todd Roberta M. O’Connor |
| author_sort | Alexis Cotto-Rosario |
| collection | DOAJ |
| description | New therapeutic agents for cryptosporidiosis are a critical medical need. The marine organic compound, tartrolon E (trtE), is highly effective against multiple apicomplexan parasites, including <i>Cryptosporidium</i>. Understanding the mechanism of action of trtE is required to advance in the drug development pipeline. Here, we validate using Nluc <i>C. parvum</i> parasites for the study of trtE and pinpoint the life stage targeted by trtE. Results show that trtE kills Nluc and wild type <i>C. parvum</i> with equal efficiency, confirming the use of the Nluc <i>C. parvum</i> to study this compound. Results revealed that trtE kills the parasite within an hour of treatment and while the compound has no effect on viability of sporozoites, trtE does inhibit establishment of infection. Targeting treatment at particular life cycle stages demonstrated that trtE is effective against asexual of the parasite but has reduced efficacy against mature sexual stages. Gene expression analysis shows that trtE inhibits the early sexual stage of the parasite. Results from these studies will aid the development of trtE as a therapeutic for cryptosporidiosis. |
| first_indexed | 2024-03-09T18:07:44Z |
| format | Article |
| id | doaj.art-34dfe1bf71944d86bb237c263c45f4b5 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T18:07:44Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-34dfe1bf71944d86bb237c263c45f4b52023-11-24T09:17:24ZengMDPI AGMicroorganisms2076-26072022-11-011011226010.3390/microorganisms10112260The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i>Alexis Cotto-Rosario0Emma Y. D. Miller1Fernanda G. Fumuso2Jason A. Clement3Matthew J. Todd4Roberta M. O’Connor5Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USABaruch S. Blumberg Institute, Doylestown, PA 18902, USABaruch S. Blumberg Institute, Doylestown, PA 18902, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USANew therapeutic agents for cryptosporidiosis are a critical medical need. The marine organic compound, tartrolon E (trtE), is highly effective against multiple apicomplexan parasites, including <i>Cryptosporidium</i>. Understanding the mechanism of action of trtE is required to advance in the drug development pipeline. Here, we validate using Nluc <i>C. parvum</i> parasites for the study of trtE and pinpoint the life stage targeted by trtE. Results show that trtE kills Nluc and wild type <i>C. parvum</i> with equal efficiency, confirming the use of the Nluc <i>C. parvum</i> to study this compound. Results revealed that trtE kills the parasite within an hour of treatment and while the compound has no effect on viability of sporozoites, trtE does inhibit establishment of infection. Targeting treatment at particular life cycle stages demonstrated that trtE is effective against asexual of the parasite but has reduced efficacy against mature sexual stages. Gene expression analysis shows that trtE inhibits the early sexual stage of the parasite. Results from these studies will aid the development of trtE as a therapeutic for cryptosporidiosis.https://www.mdpi.com/2076-2607/10/11/2260antiparasitic compoundcryptosporidiosis<i>Cryptosporidium</i>drug candidateslife cycle stagesmarine natural products |
| spellingShingle | Alexis Cotto-Rosario Emma Y. D. Miller Fernanda G. Fumuso Jason A. Clement Matthew J. Todd Roberta M. O’Connor The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i> Microorganisms antiparasitic compound cryptosporidiosis <i>Cryptosporidium</i> drug candidates life cycle stages marine natural products |
| title | The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i> |
| title_full | The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i> |
| title_fullStr | The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i> |
| title_full_unstemmed | The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i> |
| title_short | The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages of <i>Cryptosporidium parvum</i> |
| title_sort | marine compound tartrolon e targets the asexual and early sexual stages of i cryptosporidium parvum i |
| topic | antiparasitic compound cryptosporidiosis <i>Cryptosporidium</i> drug candidates life cycle stages marine natural products |
| url | https://www.mdpi.com/2076-2607/10/11/2260 |
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