The role of prokaryotic argonautes in resistance to type II topoisomerases poison ciprofloxacin.

Abstract

Argonaute proteins are programmable nucleases found in all domains of life. Eukaryotic argonautes (eAgos) participate in genetic regulation, antiviral response, and transposon silencing during RNA interference. Prokaryotic argonautes (pAgos) are much more diverse than eAgos and have been implicated in defense against invading genetic elements. Recently, it was shown that pAgos protect bacterial cells from a topoisomerase poison ciprofloxacin, raising a possibility that they may play a role in DNA replication and/or repair. Here, we discuss possible models of pAgo-mediated ciprofloxacin resistance. We propose that pAgos could (i) participate in chromosome decatenation as a backup to topoisomerases; (ii) participate in the processing of DNA repair intermediates formed after topoisomerase poisoning, or (iii) induce SOS response that generally affects DNA repair and antibiotic resistance. These hypotheses should guide future investigations of the involvement of pAgos in the emergence of resistance to ciprofloxacin and, possibly, other antibiotics.