New strategy on antimicrobial-resistance: inhibitors of DNA replication enzymes.

Antimicrobial resistance is found in all microorganisms and has become one of the biggest threats to global health. New antimicrobials with different action mechanisms from existing drugs are effective weapons to fight antibiotic-resistance. DNA replication universally exists in all living organisms and is a complicated process involving in multiple enzymes. Enzymes in bacterial DNA replication of initiation and elongation phases bring abundant targets for antimicrobial development as they are conserved and indispensable. In this review, enzyme inhibitors of DNA helicase, DNA primase, topoisomerases, DNA polymerase and DNA ligase were discussed. Special attentions were paid to structures, activities and action modes of these enzyme inhibitors to find potential drugs which can be further developed into clinic. Also, this review can provide clues for developing more effective antimicrobials.