Type III secretion system ATPase (SctN) (T3SS ATPase)

The Type III secretion system (T3SS) ATPase is a highly conserved enzyme essential for the virulence of numerous pathogenic Gram-negative bacteria, including Salmonella, Pseudomonas, and Shigella [1]. It belongs to the AAA+ family of ATPases and is responsible for providing the metabolic energy required to unfold and translocate effector proteins through the T3SS needle complex into host cells [2]. In the context of flagellar assembly, the homologous ATPase (FliI) powers the export of flagellar components required for bacterial motility [5]. Because these ATPases are critical for the delivery of virulence factors but are not required for basic bacterial survival, they represent promising targets for anti-virulence therapies that disarm pathogens without exerting the strong selective pressure for resistance seen with traditional antibiotics [4]. Current drug discovery efforts focus on small molecules that inhibit the catalytic activity or the essential hexameric oligomerization of the ATPase subunits [1, 2]. Sources: [1] Gao, X. et al. (2018) Front. Microbiol.; [2] Case, H. B. et al. (2020) Antibiotics; [3] UniProt (P0A1B3, O31043); [4] Burgess, E. R. et al. (2016) Expert Opin. Drug Discov.; [5] Minamino, T. & Namba, K. (2008) Nature.

Other names

Flagellar export ATPase (FliI)SctNFliIEscNInvCHrpNVscNYscNAAA+ ATPaseInjectisome ATPase

Inhibition of ATP hydrolysis activity, disruption of hexameric oligomerization, and blockade of effector protein translocation through the secretion channel.