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,...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013207 |
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| Summary: | 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. |
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| ISSN: | 1553-7366 1553-7374 |