SPARHA represents a two-component defense system based on a suicidal cellular response, in which activation of the HNH effector by the pAgo sensor leads to filament formation, promoting efficient degradation of invading nucleic acids.

In cells, SPARHA is activated in the presence of invaders, cleaving cellular DNA and conferring protection to the bacterial population via an abortive infection mechanism.

Target DNA recognition induces conformational changes of SPARHA, freeing the HNH domains and promoting their dimerization. Subsequent association of HNH dimers leads to formation of right-handed HNH-pAgo filaments containing dimeric active sites capable of double-stranded DNA cleavage.