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PasT of Escherichia coli sustains antibiotic tolerance and aerobic respiration as a bacterial homolog of mitochondrial Coq10

Fino, Cinzia and Vestergaard, Martin and Ingmer, Hanne and Pierrel, Fabien and Gerdes, Kenn and Harms, Alexander. (2020) PasT of Escherichia coli sustains antibiotic tolerance and aerobic respiration as a bacterial homolog of mitochondrial Coq10. MicrobiologyOpen, 9 (8). e1064.

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Abstract

Antibiotic-tolerant persisters are often implicated in treatment failure of chronic and relapsing bacterial infections, but the underlying molecular mechanisms have remained elusive. Controversies revolve around the relative contribution of specific genetic switches called toxin-antitoxin (TA) modules and global modulation of cellular core functions such as slow growth. Previous studies on uropathogenic Escherichia coli observed impaired persister formation for mutants lacking the pasTI locus that had been proposed to encode a TA module. Here, we show that pasTI is not a TA module and that the supposed toxin PasT is instead the bacterial homolog of mitochondrial protein Coq10 that enables the functionality of the respiratory electron carrier ubiquinone as a "lipid chaperone." Consistently, pasTI mutants show pleiotropic phenotypes linked to defective electron transport such as decreased membrane potential and increased sensitivity to oxidative stress. We link impaired persister formation of pasTI mutants to a global distortion of cellular stress responses due to defective respiration. Remarkably, the ectopic expression of human coq10 largely complements the respiratory defects and decreased persister levels of pasTI mutants. Our work suggests that PasT/Coq10 has a central role in respiratory electron transport that is conserved from bacteria to humans and sustains bacterial tolerance to antibiotics.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Jenal) > Molecular Microbiology (Harms)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal) > Molecular Microbiology (Harms)
UniBasel Contributors:Harms, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2045-8827
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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edoc DOI:
Last Modified:24 Nov 2021 16:34
Deposited On:24 Nov 2021 16:34

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