Two Cryptic Self-Resistance Mechanisms in Streptomyces tenebrarius Reveal Insights into the Biosynthesis of Apramycin.

Apramycin is a clinically promising aminoglycoside antibiotic (AGA). To date, mechanisms underlying the biosynthesis and self-resistance of apramycin remain largely unknown. Here we report that apramycin biosynthesis proceeds through unexpected phosphorylation, deacetylation, and dephosphorylation steps, in which a novel aminoglycoside phosphotransferase (AprU), a putative creatinine amidohydrolase (AprP), and an alkaline phosphatase (AprZ) are involved. Biochemical characterization revealed that AprU specifically phosphorylates 5-OH of a pseudotrisaccharide intermediate, whose N-7' acetyl group is subsequently hydrolyzed by AprP. AprZ is located extracellularly where it removes the phosphate group from a pseudotetrasaccharide intermediate, leading to the maturation of apramycin. Intriguingly, 7'-N-acetylated and 5-O-phosphorylated apramycin that were accumulated in ΔaprU and ΔaprZ respectively exhibited significantly reduced antibacterial activities, implying Streptomyces tenebrarius employs C-5 phosphorylation and N-7' acetylation as two strategies to avoid auto-toxicity. Significantly, this study provides insight into the design of new generation AGAs to circumvent the emergence of drug-resistant pathogens.

[Wrist arthroscopic treatment of Die-punch fracture of distal radius].

OBJECTIVE: To evaluate the effect of open reduction assisted by wrist arthroscopy in the treatment of Diepunch fracture of the distal radius. METHODS: The clinical data of 50 patients with die punch fracture of distal radius from December 2015 to May 2017 were analyzed retrospectively, including 31 males and 19 females, aged 20 to 45 (34.12±2.56) years. All patients were treated with open reduction and internal fixation of volar plate through volar approach under the assistance of wrist arthroscope. The range of wrist movement and Cooney wrist function score before and after treatment were compared. RESULTS: All patients were followed up with an average of 18 months. DR scan showed that all fractures healed and no shortening of radial axis. Three cases of incision infection occurred and disappeared after treatment. At 18 months after operation, the range of wrist movement was significantly larger than that before operation (P<0.05) . At 18 months after operation, Cooney wrist function score was higher than that before operation (P<0.05) , excellent in 33 cases, good in 13 cases, fair in 3 cases and poor in 1 case. CONCLUSION: The treatment of die punch fracture of the distal radius with open reduction assisted by arthroscopy can restore the flatness of the joint surface, promote the recovery of the function of the wrist joint quickly, and has high safety, which is worth popularizing.