Iron Starvation Conditions Upregulate Type IV Secretion System, Transcription Factor and Genes Family through the Master Regulatory Protein ErxR.

is an obligatory intracellular bacterium that causes heartwater, a fatal disease in ruminants. Due to its intracellular nature, requires a set of specific virulence factors, such as the type IV secretion system (T4SS), and outer membrane proteins (Map proteins) in order to avoid and subvert the host's immune response. Several studies have been conducted to understand the regulation of the T4SS or outer membrane proteins, in , but no integrated approach has been used to understand the regulation of pathogenicity determinants in response to environmental cues. Iron is known to be a key nutrient for bacterial growth both in the environment and within hosts. In this study, we experimentally demonstrated the regulation of , and genes by the newly identified master regulator ErxR (for epression egulator). We also analyzed the effect of iron depletion on the expression of gene transcription factor, T4SS and genes clusters in . We show that exposure of to iron starvation induces and subsequently , and genes. Our results reveal tight co-regulation of T4SS and genes via the ErxR regulatory protein at the transcriptional level, and, for the first time link genes to the virulence function , thereby advancing our understanding of infection process. These results suggest that is able to sense changes in iron concentrations in the environment and to regulate the expression of virulence factors accordingly.