Inhibition of Replication Fork Formation and Progression: Targeting the Replication Initiation and Primosomal Proteins

Over 1.2 million deaths are attributed to multi-drug-resistant (MDR) bacteria each year. Persistence of MDR bacteria is primarily due to the molecular mechanisms that permit fast replication and rapid evolution. As many pathogens continue to build resistance genes, current antibiotic treatments are being rendered useless and the pool of reliable treatments for many MDR-associated diseases is thus shrinking at an alarming rate. In the development of novel antibiotics, DNA replication is still a largely underexplored target. This review summarises critical literature and synthesises our current understanding of DNA replication initiation in bacteria with a particular focus on the utility and applicability of essential initiation proteins as emerging drug targets. A critical evaluation of the specific methods available to examine and screen the most promising replication initiation proteins is provided.

Automated summary

Over 1.2 million deaths are caused by multi-drug-resistant bacteria each year, as a result of their fast replication and rapid evolution. The accumulation of resistance genes in pathogens has made current antibiotic treatments ineffective, leading to a decrease in reliable treatment options for MDR-associated diseases. This review provides a critical evaluation of DNA replication initiation in bacteria and highlights the potential of essential initiation proteins as emerging drug targets. It also examines the available methods to study and screen promising replication initiation proteins.