Evidence for a Putative Regulatory System Consisting of an ECF σE-Type Factor, LIC_12757, and a FecR-like σ Factor Regulator, LIC_12756, in the Pathogenic Spirochaetes Leptospira interrogans

ECF σ factors, which constitute the most abundant and diverse group of the σ⁷⁰-family, are important signal response regulatory proteins in bacterial adaptative responses to harsh environmental changes and for bacterial survival. Their activity is commonly controlled by specific and reversible interactions with their cognate anti-σ factors (soluble or transmembrane proteins), which directly or indirectly sense the environmental signals and transmit them to their partner σ factor. The genome of pathogenic <i>L. interrogans</i> is predicted to encode 11 ECF σ^E-type factors and more than 30 regulators predicted as anti-σ factors, anti-anti-σ factors, and regulators of anti-anti-σ factors. We have recently demonstrated that one of the <i>L. interrogans</i> ECF σ factors, i.e., LIC_12757, indeed functions as a transcriptional factor and is autoregulated at the transcriptional level. This study is a next step towards determining key aspects of LIC_12757 functioning in <i>Leptospira</i>. By using genetic and proteomic approaches, we provide strong evidence that the LIC_12757 activity is controlled via interactions with its putative FecR-like regulator, LIC_12756. We also demonstrate that LIC_12756 exhibits not only an anti-σ activity but also acts as a positive regulator of LIC_12757 in the presence of specific environmental cues. Interestingly, we found that the nutrient-limiting conditions, including iron deficiency, may act as specific signals for the LIC_12757 activation. In conclusion, we identified the <i>L. interrogans</i> regulatory system consisting of an ECF σ factor, LIC_12757, and a FecR-like regulator, LIC_12756, which is most likely involved in the response of pathogenic <i>Leptospira</i> to iron and nutrient limitation, and thus also likely involved in their response to host-induced stress.