A fungal biofilm reactor based on metal structured packing improves the quality of a Gla::GFP fusion protein produced by Aspergillus oryzae.

Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-state-related physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilm reactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae. The biofilm reactor comprises a metal structured packing allowing the attachment of the fungal biomass. Since the production of the target protein is under the control of the promoter glaB, specifically induced in solid-state fermentation, the biofilm mode of culture is expected to enhance the global productivity. Although production of the target protein was enhanced by using the biofilm mode of culture, we also found that fusion protein production is also significant when the submerged mode of culture is used. This result is related to high shear stress leading to biomass autolysis and leakage of intracellular fusion protein into the extracellular medium. Moreover, 2-D gel electrophoresis highlights the preservation of fusion protein integrity produced in biofilm conditions. Two fungal biofilm reactor designs were then investigated further, i.e. with full immersion of the packing or with medium recirculation on the packing, and the scale-up potentialities were evaluated. In this context, it has been shown that full immersion of the metal packing in the liquid medium during cultivation allows for a uniform colonization of the packing by the fungal biomass and leads to a better quality of the fusion protein.

Update on counterfeit antibiotics worldwide; public health risks.

Antibiotics are the most counterfeited medicines and account for 28% of global counterfeit medicines. Counterfeit antibiotics are estimated at 5% of the global antibiotic market. No area in the world seems to be spared from counterfeiting of antibiotics. However, these are rare in developed countries, whereas the strong demand for antibiotics in emerging countries creates a highly attractive market for counterfeiters. Thus, 78% of counterfeit antibiotics come from South-East Asia and their destination is mainly emerging countries (South-East Asia: 44%; sub-Saharan Africa: 30%; Europe, North America: 9%; others: 16%). Counterfeit antibiotics are antibiotics that have been commonly used for years (beta-lactams: 50%; quinolones: 12%; macrolides, lincosamides, and synergistins: 1%; cyclins: 7%; others: 20%). The main counterfeit formulations (77%) concern oral administration (tablets, syrup, capsules) whereas injected drugs account for only 17% of counterfeit formulations, and eye drops and ointments 6%. The kind of counterfeiting for antibiotics is similar to that of other drugs (no active ingredients: 43%; bad quality: 24%; insufficient quantity of active ingredients: 21%; wrong active ingredients: 7%; counterfeit packaging: 5%). Beyond the harmful effects for patients, counterfeit medicines favor the emergence of bacterial resistance with a worldwide impact. Great efforts have been made to fight global counterfeiting of medicines since 1985.