Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression
Chlamydia trachomatis is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are un...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/98409 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841525350731874304 |
|---|---|
| author | Vandana Singh Scot P Ouellette |
| author_facet | Vandana Singh Scot P Ouellette |
| author_sort | Vandana Singh |
| collection | DOAJ |
| description | Chlamydia trachomatis is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown. EBs and RBs have distinctive characteristics that distinguish them, including their size, infectivity, proteome, and transcriptome. Intriguingly, they also differ in their overall redox status as EBs are oxidized and RBs are reduced. We hypothesize that alterations in redox may serve as a trigger for secondary differentiation. To test this, we examined the function of the primary antioxidant enzyme alkyl hydroperoxide reductase subunit C (AhpC), a well-known member of the peroxiredoxins family, in chlamydial growth and development. Based on our hypothesis, we predicted that altering the expression of ahpC would modulate chlamydial redox status and trigger earlier or delayed secondary differentiation. Therefore, we created ahpC overexpression and knockdown strains. During ahpC knockdown, ROS levels were elevated, and the bacteria were sensitive to a broad set of peroxide stresses. Interestingly, we observed increased expression of EB-associated genes and concurrent higher production of EBs at an earlier time in the developmental cycle, indicating earlier secondary differentiation occurs under elevated oxidation conditions. In contrast, overexpression of AhpC created a resistant phenotype against oxidizing agents and delayed secondary differentiation. Together, these results indicate that redox potential is a critical factor in developmental cycle progression. For the first time, our study provides a mechanism of chlamydial secondary differentiation dependent on redox status. |
| format | Article |
| id | doaj-art-13629a30ca924a4697ac8ea592c3785d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-13629a30ca924a4697ac8ea592c3785d2025-01-17T13:52:52ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.98409Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progressionVandana Singh0https://orcid.org/0000-0001-5368-6200Scot P Ouellette1https://orcid.org/0000-0002-3721-6839Department of Pathology, Microbiology, and Immunology, College of Medicine, University of Nebraska Medical Center, Omaha, United StatesDepartment of Pathology, Microbiology, and Immunology, College of Medicine, University of Nebraska Medical Center, Omaha, United StatesChlamydia trachomatis is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown. EBs and RBs have distinctive characteristics that distinguish them, including their size, infectivity, proteome, and transcriptome. Intriguingly, they also differ in their overall redox status as EBs are oxidized and RBs are reduced. We hypothesize that alterations in redox may serve as a trigger for secondary differentiation. To test this, we examined the function of the primary antioxidant enzyme alkyl hydroperoxide reductase subunit C (AhpC), a well-known member of the peroxiredoxins family, in chlamydial growth and development. Based on our hypothesis, we predicted that altering the expression of ahpC would modulate chlamydial redox status and trigger earlier or delayed secondary differentiation. Therefore, we created ahpC overexpression and knockdown strains. During ahpC knockdown, ROS levels were elevated, and the bacteria were sensitive to a broad set of peroxide stresses. Interestingly, we observed increased expression of EB-associated genes and concurrent higher production of EBs at an earlier time in the developmental cycle, indicating earlier secondary differentiation occurs under elevated oxidation conditions. In contrast, overexpression of AhpC created a resistant phenotype against oxidizing agents and delayed secondary differentiation. Together, these results indicate that redox potential is a critical factor in developmental cycle progression. For the first time, our study provides a mechanism of chlamydial secondary differentiation dependent on redox status.https://elifesciences.org/articles/98409Chlamydiadevelopmental cycledifferentiationredoxAhpCCRISPRi |
| spellingShingle | Vandana Singh Scot P Ouellette Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression eLife Chlamydia developmental cycle differentiation redox AhpC CRISPRi |
| title | Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression |
| title_full | Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression |
| title_fullStr | Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression |
| title_full_unstemmed | Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression |
| title_short | Altering the redox status of Chlamydia trachomatis directly impacts its developmental cycle progression |
| title_sort | altering the redox status of chlamydia trachomatis directly impacts its developmental cycle progression |
| topic | Chlamydia developmental cycle differentiation redox AhpC CRISPRi |
| url | https://elifesciences.org/articles/98409 |
| work_keys_str_mv | AT vandanasingh alteringtheredoxstatusofchlamydiatrachomatisdirectlyimpactsitsdevelopmentalcycleprogression AT scotpouellette alteringtheredoxstatusofchlamydiatrachomatisdirectlyimpactsitsdevelopmentalcycleprogression |