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

Previous work on antibiotic ‐tolerant persisters of pathogenicEscherichia coli highlighted the role of PasT, described as a toxin of a toxin –antitoxin system, in their resilience. Here, we show that PasT is not a toxin but rather the bacterial homolog of mitochondrial Coq10 that guides the electron carrier ubiquinone in respiratory electron transport. Consistently,pasT mutants of pathogenicE.  coli andSalmonella Typhimurium show pleiotropic phenotypes of defective respiration including impaired persister formation that can largely be complemented by human Coq10. AbstractAntibiotic ‐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 uropathogenicEscherichia coli observed impaired persister formation for mutants lacking thepasTI locus that had been proposed to encode a TA module. Here, we show thatpasTI 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 pot...
Source: MicrobiologyOpen - Category: Microbiology Authors: Tags: ORIGINAL ARTICLE Source Type: research