A Pivotal Role for Mycobactin/mbtE in Growth and Adaptation of Mycobacterium abscessus.

Mycobacterium abscessus is an emerging pathogen that critically depends on iron for growth and pathogenesis. The acquisition of iron in Mycobacterium tuberculosis is governed by siderophores called mycobactins, synthesized by the mbt gene cluster, but the role of this gene cluster in the adaption of M. abscessus to iron limitation is not characterized. We identified an M. abscessus Tn_mutant with interruption of the mbtE gene (MAB_2248c), a central component of mycobactin biosynthesis. We tested this isolate growth characteristic, dependency on supplements, and transcriptomic response, comparing it to the response of wild-type (WT) bacteria in iron-limiting conditions. We also compare the structure of the mbt gene cluster across several mycobacteria. The Tn_mbtE mutant had a substantial, but not absolute, growth defect, which was more substantial in iron-limited media. Supplementation with mycobactin-J, hemin, blood, and surprisingly, albumin, salvaged the poor growth. Similarly, secreted mature (carboxy)-mycobactins from WT bacteria rescued the Tn_mbtE mutant during iron deprivation. The transcriptomic response of the Tn_mbtE mutant involved the upregulation of genes known to be implicated in iron homeostasis and was comparable to that of WT bacteria grown in iron-limiting conditions. Interestingly, the response was not identical to the response of M. tuberculosis to iron limitation. The mbt gene cluster and mycobactins play important roles in the physiology of M. abscessus. (Carboxy)-mycobactin is secreted from WT bacteria and can serve as "public good." The role of several iron-homeostasis related genes (like ideR) may differ between M. abscessus and Mtb. IMPORTANCE Mycobacterium abscessus is an emerging human pathogen belonging to the nontuberculous mycobacteria (NTM) family, causing severe pulmonary disease in compromised individuals. How this bacterium acquires iron is poorly understood. Here, we provide the first characterization of the role(s) the mbtE gene required for the biosynthesis of siderophore mycobactin in M. abscessus. We show that the gene mbtE is required for growth during iron deprivation and can be compensated by several supplements, including, surprisingly, albumin. We also show the transcriptomic response of the mbtE-mutant is comparable to the response of the parental strain to iron starvation and seems different from the response of M. tuberculosis. These results indicate the importance of studying mycobactin in M. abscessus and NTM strains. Understanding this pathway is central to understanding the acquisition of iron within hosts and its role in pathogenesis, which in turn may facilitate the development of antimycobacterial therapeutics.

Recycling of high purity selenium from CIGS solar cell waste materials.

Copper indium gallium diselenide (CIGS) is a promising material in thin film solar cell production. To make CIGS solar cells more competitive, both economically and environmentally, in comparison to other energy sources, methods for recycling are needed. In addition to the generally high price of the material, significant amounts of the metals are lost in the manufacturing process. The feasibility of recycling selenium from CIGS through oxidation at elevated temperatures was therefore examined. During oxidation gaseous selenium dioxide was formed and could be separated from the other elements, which remained in solid state. Upon cooling, the selenium dioxide sublimes and can be collected as crystals. After oxidation for 1h at 800°C all of the selenium was separated from the CIGS material. Two different reduction methods for reduction of the selenium dioxide to selenium were tested. In the first reduction method an organic molecule was used as the reducing agent in a Riley reaction. In the second reduction method sulphur dioxide gas was used. Both methods resulted in high purity selenium. This proves that the studied selenium separation method could be the first step in a recycling process aimed at the complete separation and recovery of high purity elements from CIGS.

Neotrofin increases heme oxygenase-1 selectively in neurons.

There is evidence that heme oxygenase plays a role in cellular defense against reactive oxygen species and thereby has neuroprotective effects. We examined the interaction of Neotrofin, a cognitive-enhancing and neuroprotective drug, with the heme oxygenase system. In adult rats, both a single administration or seven daily injections of Neotrofin at 10, 30 or 100 mg/kg intraperitoneally increased HO-1 immunoreactivity in neurons of the hippocampal formation and its connections including CA1-4, fornix, septal nuclei, hippocampal commissure, septohippocampal nucleus, fimbria, anteroventral thalamic nucleus, frontal and parietal cortex. Prominent HO-1 staining of neuronal cells in the proximity of blood vessels and circumventricular organs was also observed. Increasing doses of Neotrofin resulted in an increase in the number of neuronal populations expressing HO-1 with 100 mg/kg evoking a widespread neuronal cell response in brain. Quantification by ELISA confirmed that intraperitoneal administration of 100 mg/kg Neotrofin caused a significant increase in HO-1 protein expression in the hippocampus. The increase was evident by 6 h post-injection, peaked at 24 h with a 4-fold increase, and persisted for at least 48 h. Similarly, oral administration of 100 mg/kg Neotrofin produced a 5-fold increase in HO-1 protein 24 h post-administration. The effect of Neotrofin on HO-1 appears to be at the transcriptional level, as suggested by an increase in HO-1 mRNA levels. Neotrofin treatment was also associated with a significant increase in HO-2 mRNA levels in whole brain homogenate. These data may explain the neuroprotective effects of Neotrofin in models of excitotoxic neuronal injury.