Adventures with the Argonautes
Animals, plants, and other eukaryotes use Argonaute proteins, guided by short RNA sequences, to defend cells against transposons and viruses. Many bacterial genomes also encode Argonaute proteins, but their functions remain unknown. The best studied eubacterial Argonaute is the DNA-guided protein TtAgo from Thermus thermophilus. TtAgo has been proposed to defend T. thermophilus against transformation by DNA plasmids, a function analogous to transposon defense in eukaryotes. I will describe our discovery that in T. thermophilus, TtAgo confers resistance to the antibiotic ciprofloxacin. Ciprofloxacin blocks bacterial growth by inhibiting the enzyme gyrase, which separates the topologically linked chromosomes that result from replicating circular DNA. TtAgo provides an alternative route to chromosome decatenation in the absence of functional gyrase, allowing the bacterium to finish replicating its circular genome. The mechanism of TtAgo DNA guide acquisition and the in vivo function of TtAgo will be presented.
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