Infection Rewires the Transcriptome, Highlighting a Class of Sirtuin Genes.

is an environmental bacterium that has evolved to survive predation by soil and water amoebae such as , and this has inadvertently led to the ability of to survive and replicate in human cells. causes Legionnaire's Disease, with human exposure occurring via the inhalation of water aerosols containing both amoebae and the bacteria. These aerosols originate from aquatic biofilms found in artifical water sources, such as air-conditioning cooling towers and humidifiers. In these man-made environments, supports intracellular replication, thereby promoting persistence and dissemination of the bacteria and providing protection from external stress. Despite this close evolutionary relationship, very little is known about how responds to infection. In this study, we examined the global transcriptional response of to infection. We compared infected with wild type to infected with an isogenic Δ mutant strain, which is unable to replicate intracellularly. We showed that underwent clear morphological and transcriptional rewiring over the course of infection. Through improved annotation of the genome, we determined that these transcriptional changes primarily involved biological processes utilizing small GTPases, including cellular transport, signaling, metabolism and replication. In addition, a number of sirtuin-encoding genes in were found to be conserved and upregulated during infection. Silencing of sirtuin gene, (ACA1_153540) resulted in the inhibition of cell proliferation during infection and reduced replication. Overall our findings identified several biological pathways in amoebae that may support replication and proliferation in environmental conditions.