Bacterial topoisomerase IV (Topo IV) (Topo IV)

Bacterial topoisomerase IV is an essential type II topoisomerase enzyme, typically composed of two subunits (ParC and ParE in Gram-negative bacteria, or GrlA and GrlB in Gram-positive bacteria), that plays a critical role in bacterial DNA replication and chromosome segregation (UniProt Consortium, 2023). Its primary biological function is the decatenation, or unlinking, of daughter chromosomes following DNA replication, which ensures that genetic material is correctly partitioned into daughter cells during division (PubMed, PMID: 24513976). While it shares structural similarities with DNA gyrase, topoisomerase IV is uniquely specialized for resolving topological knots and links in the circular bacterial genome. This enzyme serves as a primary therapeutic target for fluoroquinolone antibiotics, which act by binding to the enzyme-DNA complex and stabilizing the covalent cleavage intermediate (StatPearls, NBK547703). This stabilization prevents the religation of DNA strands, leading to the accumulation of double-strand breaks and subsequent bacterial cell death. Clinical resistance often develops through mutations in the quinolone-resistance determining regions (QRDR) of the parC and parE genes, making it a focal point for monitoring antibiotic efficacy (PubMed, PMID: 11029450).

Other names

DNA topoisomerase IVParC-ParE complexGrlA-GrlB complexTopoisomerase 4Type II topoisomeraseBacterial topoisomerase IV–DNA complex

Fluoroquinolones bind to the topoisomerase IV-DNA complex, stabilizing the covalent enzyme-DNA intermediate known as the cleavage complex. This action prevents the religation of DNA strands, leading to the accumulation of double-strand breaks, inhibition of DNA replication, and ultimately bacterial cell death (Aldred et al., 2014; Bush et al., 2015).