Mycobacterium tuberculosis DNA topoisomerase IV (Topo IV) (Topo IV)

Mycobacterium tuberculosis DNA topoisomerase IV is a protein complex that is notably absent from the Mycobacterium tuberculosis (Mtb) genome, making it an invalid therapeutic target (Cole et al., 1998, Nature). In most bacterial species, DNA topoisomerase IV is a type II topoisomerase composed of ParC and ParE subunits responsible for decatenating daughter chromosomes during DNA replication. However, Mtb is unique in that it lacks the parC and parE genes and instead utilizes a single type II topoisomerase, DNA gyrase, to perform both supercoiling and decatenation functions (Manjunatha et al., 2002, Nucleic Acids Research). While fluoroquinolones are often described as dual-target inhibitors of both DNA gyrase and topoisomerase IV in other bacteria, their bactericidal activity in Mtb is mediated solely through the inhibition of DNA gyrase (Aubry et al., 2006, Antimicrobial Agents and Chemotherapy). Consequently, any reference to topoisomerase IV as a target in Mtb is biologically inaccurate. This absence of a second type II topoisomerase simplifies the target landscape for Mtb but also means that resistance mutations in DNA gyrase can more readily lead to high-level fluoroquinolone resistance (Makarov et al., 2007, Journal of Biological Chemistry).

Other names

Topo IVParC-ParE complexType II topoisomerase IVTopoisomerase 4

Not applicable due to the absence of the target in Mycobacterium tuberculosis.