Mycobacterial Topoisomerase IV (Topo IV)

Mycobacterial Topoisomerase IV is a target that is notably absent in the genus Mycobacterium, including the pathogen Mycobacterium tuberculosis (Aubry et al., 2006). Unlike most other bacteria which utilize two type II topoisomerases—DNA gyrase for supercoiling and Topoisomerase IV for decatenation—mycobacteria possess only DNA gyrase, which performs both essential functions (Manjunatha et al., 2002). Consequently, while fluoroquinolone antibiotics like moxifloxacin and gatifloxacin are effective against mycobacterial infections, they exert their antibacterial activity solely by inhibiting DNA gyrase (Mayer & Janin, 2014). The lack of Topoisomerase IV in mycobacteria is a significant evolutionary distinction that simplifies the target profile for drug development but also places the entire burden of topological maintenance on a single enzyme (Cole et al., 1998). Therefore, any drug discovery efforts directed specifically at 'Mycobacterial Topoisomerase IV' would be misplaced, as the enzyme does not exist in these organisms. Resistance to fluoroquinolones in mycobacteria is thus mediated exclusively through mutations in DNA gyrase rather than through the dual-target mutations seen in other bacterial species (Aubry et al., 2006). This unique biological feature makes DNA gyrase an exceptionally critical target for anti-tubercular therapy (Blower et al., 2016).

Other names

ParC-ParE complexType II topoisomerase

Inhibition of DNA re-ligation following cleavage, leading to lethal double-strand breaks and bacterial cell death.