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Published on: May 24, 2024
Growth of Chlamydia pneumoniae Is Enhanced in Cells with Impaired Mitochondrial Function
Nadja Käding1, Inga Kaufhold1, Constanze Müller2
1Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
Abstract:
Effective growth and replication of obligate intracellular pathogens depend on host cell metabolism. How this is connected to host cell mitochondrial function has not been studied so far. Recent studies suggest that growth of intracellular bacteria such as Chlamydia pneumoniae is enhanced in a low oxygen environment, arguing for a particular mechanistic role of the mitochondrial respiration in controlling intracellular progeny. Metabolic changes in C. pneumoniae infected epithelial cells were analyzed under normoxic (O2 ≈ 20%) and hypoxic conditions (O2 < 3%). We observed that infection of epithelial cells with C. pneumoniae under normoxia impaired mitochondrial function characterized by an enhanced mitochondrial membrane potential and ROS generation. Knockdown and mutation of the host cell ATP synthase resulted in an increased chlamydial replication already under normoxic conditions. As expected, mitochondrial hyperpolarization was observed in non-infected control cells cultured under hypoxic conditions, which was beneficial for C. pneumoniae growth. Taken together, functional and genetically encoded mitochondrial dysfunction strongly promotes intracellular growth of C. pneumoniae.
Insights
Mitochondrial dysfunction enhances intracellular bacteria growth. Impaired host cell mitochondrial function, particularly ATP synthase, boosts Chlamydia pneumoniae replication, even under normal oxygen levels.
Area of Science:
- Cell Biology
- Microbiology
- Mitochondrial Biology
Background:
- Obligate intracellular pathogen replication relies on host cell metabolism.
- The link between host mitochondrial function and pathogen growth is largely unexplored.
- Chlamydia pneumoniae growth is enhanced in low oxygen, suggesting a role for mitochondrial respiration.
Purpose of the Study:
- To investigate the impact of host cell mitochondrial function on Chlamydia pneumoniae replication.
- To analyze metabolic changes in infected epithelial cells under normoxic and hypoxic conditions.
Main Methods:
- Epithelial cells infected with Chlamydia pneumoniae were cultured under normoxic and hypoxic conditions.
- Mitochondrial membrane potential and ROS generation were measured.
- Host cell ATP synthase was inhibited via knockdown and mutation.
Main Results:
- Chlamydia pneumoniae infection impaired mitochondrial function under normoxia, increasing membrane potential and ROS.
- Inhibition of host ATP synthase significantly increased chlamydial replication under normoxia.
- Mitochondrial hyperpolarization under hypoxia benefited Chlamydia pneumoniae growth.
Conclusions:
- Functional and genetic mitochondrial dysfunction promotes intracellular Chlamydia pneumoniae growth.
- Targeting host mitochondrial pathways could be a strategy against Chlamydia pneumoniae infections.
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