Improved Plaque Assay Identifies a Novel Anti-Chlamydia Ceramide Derivative with Altered Intracellular Localization
| Autor: | Dagmar Heuer, Andrea Martini, Sophia Koch, Sebastian Banhart, Christoph Arenz, Kazimierz Madela, Essa M. Saied, Lukas Aeberhard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.drug_class
Antibiotics Human pathogen Chlamydia trachomatis Microbial Sensitivity Tests Biology medicine.disease_cause Ceramides Mice Cell Line Tumor Drug Discovery medicine Animals Humans Pharmacology (medical) Microbiome Pharmacology Virus quantification Sphingolipids Chlamydia Clinical Laboratory Techniques Biological Transport Chlamydia Infections medicine.disease Virology Sphingolipid Anti-Bacterial Agents Infectious Diseases Trachoma Susceptibility Immunology lipids (amino acids peptides and proteins) HeLa Cells |
| Popis: | Chlamydia trachomatis is a medically important human pathogen causing different diseases, including trachoma, the leading cause of preventable blindness in developing countries, and sexually transmitted infections that can lead to infertility and ectopic pregnancies. There is no vaccine against C. trachomatis at present. Broad-spectrum antibiotics are used as standard therapy to treat the infection but have unwanted side effects, such as inducing persistent or recurring infections and affecting the host microbiome, necessitating the development of novel anti- Chlamydia therapies. Here, we describe the establishment of a robust, fast, and simple plaque assay using liquid overlay medium (LOM) for the identification of anti- Chlamydia compounds. Using the LOM plaque assay, we identified nitrobenzoxadiazole (NBD)-labeled 1- O -methyl-ceramide-C 16 as a compound that efficiently inhibits C. trachomatis replication without affecting the viability of the host cell. Further detailed analyses indicate that 1- O -methyl-NBD-ceramide-C 16 acts outside the inclusion. Thereby, 1- O -methyl-NBD-ceramide-C 16 represents a lead compound for the development of novel anti- Chlamydia drugs and furthermore constitutes an agent to illuminate sphingolipid trafficking pathways in Chlamydia infections. |
| Databáze: | OpenAIRE |
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