In summary, we identified PARP as a host target for HDT during Mtb infections, and confirmed that PARP inhibition is a promising avenue in the development of HDT against Mtb. Furthermore, our data show that also off-target kinase pharmacology of PARP inhibitors may expand the current clinical scope of PARP inhibitors and that these molecules deserve serious consideration in the development of repurposed HDT against intracellular bacterial infections. Here, PARP1 is linked to bacterial infectious disease.