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Type IV secretion systems (T4SSs) are subclassified as conjugation machines or effector translocators, according to their capacity to transmit mobile DNA elements to bacterial cells or protein effectors to eukaryotic cells. Whitaker et al. (p. 2701−2718) have repurposed the “dedicated” conjugation machine encoded by Escherichia coli pKM101 for protein transfer. This was achieved by creating chimeras of “coupling proteins” associated with the pKM101 system and effector translocators from alphaproteobacterial species. These findings advance a mechanistic understanding of T4SSs and suggest that functionally diversified T4SSs might prove useful for the targeted delivery of therapeutic protein or DNA substrates into cell types of interest.