Thiopeptides Induce Proteasome-Independent Activation of Cellular Mitophagy

Thiopeptide antibiotics are emerging clinical candidates that exhibit potent antibacterial activity against a variety of intracellular pathogens, including Mycobacterium tuberculosis (Mtb). Many thiopeptides directly inhibit bacterial growth by disrupting protein synthesis. However, recent work has shown that one thiopeptide, thiostrepton (TSR), can also induce autophagy in infected macrophages, which has the potential to be exploited for host-directed therapies against intracellular pathogens, such as Mtb. To better define the therapeutic potential of this class of antibiotics, we studied the host-directed effects of a suite of natural thiopeptides that spans five structurally diverse thiopeptide classes, as well as several analogs. We discovered that thiopeptides as a class induce selective autophagic removal of mitochondria, known as mitophagy. This activity is independent of other biological activities, such as proteasome inhibition or antibiotic activity. We also find that many thiopeptides exhibit potent activity against intracellular Mtb in macrophage infection models. However, the thiopeptide-induced mitophagy occurs outside of pathogen-containing autophagosomes and does not appear to contribute to thiopeptide control of intracellular Mtb. These results expand basic understanding of thiopeptide biology and provide key guidance for the development of new thiopeptide antibiotics and host-directed therapeutics

Effectiveness of recovered magnesium phosphates as fertilizers in neutral and slightly alkaline soils

Magnesium phosphates such as struvite (MgNH4PO4 · 6H2O) can be recovered from municipal, industrial, and agricultural wastewaters. However, limited information is available on the beneficial reuse of these recovered products; research has focused on low pH soils. Th is study determined whether recovered struvite and dittmarite (MgNH4PO4 · H2O) were effective P fertilizers in neutral to slightly alkaline soils. In addition to commercially available triple superphosphate (TSP) and certified organic rock phosphate (RP), recovered struvite, dittmarite, and a heterogeneous recovered phosphate were evaluated in a laboratory dissolution study and as fertilizers for spring wheat (Triticum aestivum L.) in a greenhouse study. Struvite and dittmarite were much more soluble than RP, but less soluble than TSP. Laboratory dissolution kinetics were fast, with most materials nearing equilibrium within 7 to 14 d. At a soil pH of 6.5, both dittmarite and struvite increased the average plant P concentration over the control. Struvite and dittmarite performance was similar to TSP. There were no significant differences in plant dry matter (DM) production or total P uptake at pH 6.5. In the limed soil (pH 7.6), many treatments had plant P concentrations significantly lower than the control, but most fertilizers increased DM production over the control; all fertilizers generally performed similarly to one another. These findings support previous work showing recovered Mg phosphates to be effective in acidic soils, and provide evidence that they are also effective in slightly alkaline soils. Recovered Mg phosphates could become a useful alternative for P fertilization in arid and semiarid environments

The 44Ti(α, p) reaction and its implication on the 44Ti yield in supernovae

Cross sections for the 44Ti(α, p)47V reaction which significantly affects the yield of 44Ti in supernovae were measured in the energy range 5.7MeV ≤ Ec.m. ≤ 9 MeV, using a beam of radioactive 44Ti. The cross sections and the deduced astrophysical reaction rates are larger than the results from theoretical calculations by about a factor of 2. The implications of this increase in the reaction rate for the search of supernovae using space-based gamma detectors are discussed

Sorting of CD4 and the SIV envelope glycoprotein in the endocytic pathway

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