Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.
Potassium (K+) is the most abundant intracellular cation, but much remains unknown regarding how K+ homeostasis is integrated with other key bacterial biology aspects. Here, we show that K+ homeostasis disruption (CeoBC K+ uptake system deletion) impedes Mycobacterium tuberculosis (Mtb) response to,...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013207 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850160088868716544 |
|---|---|
| author | Yue Chen Berge Hagopian Shumin Tan |
| author_facet | Yue Chen Berge Hagopian Shumin Tan |
| author_sort | Yue Chen |
| collection | DOAJ |
| description | Potassium (K+) is the most abundant intracellular cation, but much remains unknown regarding how K+ homeostasis is integrated with other key bacterial biology aspects. Here, we show that K+ homeostasis disruption (CeoBC K+ uptake system deletion) impedes Mycobacterium tuberculosis (Mtb) response to, and growth in, cholesterol, a critical carbon source during infection, with K+ augmenting activity of the Mtb ATPase MceG that is vital for bacterial cholesterol import. Reciprocally, cholesterol directly binds to CeoB, modulating its function, with a residue critical for this interaction identified. Finally, cholesterol binding-deficient CeoB mutant Mtb are attenuated for growth in lipid-rich foamy macrophages and in vivo colonization. Our findings raise the concept of a role for cholesterol as a key co-factor, beyond its role as a carbon source, and illuminate how changes in intrabacterial K+ levels can act as part of the metabolic adaptation critical for bacterial survival and growth in the host. |
| format | Article |
| id | doaj-art-67e545619bc64fd388b8f6eabaa2a63f |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-67e545619bc64fd388b8f6eabaa2a63f2025-08-20T02:23:15ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-05-01215e101320710.1371/journal.ppat.1013207Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.Yue ChenBerge HagopianShumin TanPotassium (K+) is the most abundant intracellular cation, but much remains unknown regarding how K+ homeostasis is integrated with other key bacterial biology aspects. Here, we show that K+ homeostasis disruption (CeoBC K+ uptake system deletion) impedes Mycobacterium tuberculosis (Mtb) response to, and growth in, cholesterol, a critical carbon source during infection, with K+ augmenting activity of the Mtb ATPase MceG that is vital for bacterial cholesterol import. Reciprocally, cholesterol directly binds to CeoB, modulating its function, with a residue critical for this interaction identified. Finally, cholesterol binding-deficient CeoB mutant Mtb are attenuated for growth in lipid-rich foamy macrophages and in vivo colonization. Our findings raise the concept of a role for cholesterol as a key co-factor, beyond its role as a carbon source, and illuminate how changes in intrabacterial K+ levels can act as part of the metabolic adaptation critical for bacterial survival and growth in the host.https://doi.org/10.1371/journal.ppat.1013207 |
| spellingShingle | Yue Chen Berge Hagopian Shumin Tan Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis. PLoS Pathogens |
| title | Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis. |
| title_full | Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis. |
| title_fullStr | Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis. |
| title_full_unstemmed | Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis. |
| title_short | Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis. |
| title_sort | cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in mycobacterium tuberculosis |
| url | https://doi.org/10.1371/journal.ppat.1013207 |
| work_keys_str_mv | AT yuechen cholesterolmetabolismandintrabacterialpotassiumhomeostasisareintrinsicallyrelatedinmycobacteriumtuberculosis AT bergehagopian cholesterolmetabolismandintrabacterialpotassiumhomeostasisareintrinsicallyrelatedinmycobacteriumtuberculosis AT shumintan cholesterolmetabolismandintrabacterialpotassiumhomeostasisareintrinsicallyrelatedinmycobacteriumtuberculosis |