Legionella para-effectors target chromatin and promote bacterial replication

Legionella pneumophilia is known to secrete more than 300 effectors via a type IV secretion system. Here, Schator et al. characterise how the chromatin modifying effectors RomA and LphD work synergistically to hijack host responses and facilitate bacterial replication. Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA) that methylates K14 of histone H3 (H3K14me3) to counteract host immune responses. However, it is not known how L. pneumophila infection catalyses H3K14 methylation as this residue is usually acetylated. Here we show that L. pneumophila secretes a eukaryotic-like histone deacetylase (LphD) that specifically targets H3K14ac and works in synergy with RomA. Both effectors target host chromatin and bind the HBO1 histone acetyltransferase complex that acetylates H3K14. Full activity of RomA is dependent on the presence of LphD as H3K14 methylation levels are significantly decreased in a increment lphD mutant. The dependency of these two chromatin-modifying effectors on each other is further substantiated by mutational and virulence assays revealing that the presence of only one of these two effectors impairs intracellular replication, while a double knockout ( increment lphD increment romA) can restore intracellular replication. Uniquely, we present evidence for para-effectors, an effector pair, that actively and coordinately modify host histones to hijack the host response. The identification of epigenetic marks modulated by pathogens has the potential to lead to the development of innovative therapeutic strategies to counteract bacterial infection and strengthening host defences.

Automated summary

Legionella pneumophilia secretes more than 300 effectors, including RomA and LphD, via a type IV secretion system. RomA methylates histone H3 at K14 to counteract host immune responses, while LphD deacetylates H3K14 to work synergistically with RomA. The two effectors target host chromatin and bind the HBO1 histone acetyltransferase complex to regulate histone modifications.