IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin

The human opportunistic pathogen Bacillus cereus belongs to the B. cereus group that includes bacteria with a broad host spectrum. The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors. Previously, an IVET strategy led to the identification of a novel B. cereus protein (IlsA, Iron-regulated leucine rich surface protein), which is specifically expressed in the insect host or under iron restrictive conditions in vitro. Here, we show that IlsA is localized on the surface of B. cereus and hence has the potential to interact with host proteins. We report that B. cereus uses hemoglobin, heme and ferritin, but not transferrin and lactoferrin. In addition, affinity tests revealed that IlsA interacts with both hemoglobin and ferritin. Furthermore, IlsA directly binds heme probably through the NEAT domain. Inactivation of ilsA drastically decreases the ability of B. cereus to grow in the presence of hemoglobin, heme and ferritin, indicating that IlsA is essential for iron acquisition from these iron sources. In addition, the ilsA mutant displays a reduction in growth and virulence in an insect model. Hence, our results indicate that IlsA is a key factor within a new iron acquisition system, playing an important role in the general virulence strategy adapted by B. cereus to colonize susceptible hosts

Modifications in basal and stress-induced hypothalamic AMP-activated protein kinase (AMPK) activity in rats chronically treated with an angiotensin II receptor blocker.

5' adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor. The role of hypothalamic AMPK in response to restraint and surgical stress has not been previously investigated. It has been recently suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating metabolic pathways including the regulation of the AMPK system. This study was thus aimed to evaluate the effects of candesartan, an angiotensin II AT1 receptor blocker drug, on hypothalamic AMPK activity under basal conditions and after restraint in conscious rats or after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in the drinking water for 2 weeks. The hypothalamic AMPK activity was determined under basal and stress conditions, using a kinase activity assay. Chronic administration of candesartan significantly increased hypothalamic AMPK activity. Hypothalamic AMPK activity was also increased by restraint stress whereas no change was observed during surgical stress under anesthesia. The high levels of hypothalamic AMPK activation observed in candesartan-treated rats were not changed by restraint stress but were reduced to control levels by anesthesia and surgery. In conclusion, chronic candesartan treatment and restraint stress in conscious rats stimulate the hypothalamic AMPK activity, whereas surgical stress under anesthesia inhibits pathways regulating the AMPK activity even in candesartan-treated rats

ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016.

Meeting abstrac