Effects of bioreactor hydrodynamics on the physiology of Streptomyces.

Streptomyces are filamentous bacteria which are widely used industrially for the production of therapeutic biomolecules, especially antibiotics. Bioreactor operating conditions may impact the physiological response of Streptomyces especially agitation and aeration as they influence hydromechanical stress, oxygen and nutrient transfer. The understanding of the coupling between physiological response and bioreactor hydrodynamics lies on a simultaneous description of the flow and transfers encountered by the bacteria and of the microbial response in terms of growth, consumption, morphology, production or intracellular signals. This article reviews the experimental and numerical works dedicated to the study of the coupling between bioreactor hydrodynamics and antibiotics producing Streptomyces. In a first part, the description of hydrodynamics used in these works is presented and then the main relations used. In a second part, the assumptions made in these works are discussed and put into emphasize. Lastly, the various Streptomyces physiological responses observed are detailed and compared.

Recognition of heat shock protein 60 epitopes in children with type 1 diabetes.

BACKGROUND: Treatment with a specific HSP60 epitope in new onset of type 1 diabetes (T1D) patients has been shown to preserve endogenous insulin production. Previously, recognition of pan HLA-DR-binding HSP60 epitopes in various autoimmune diseases was found; this study investigated recognition of these epitopes in newly diagnosed T1D patients and correlated findings to the occurrence of a partial remission. METHODS: Peripheral blood mononuclear cells of 18 children with T1D were prospectively collected at disease onset and a few months after diagnosis. Epitope-specific T-cell proliferation and cytokine production (intracellular and in culture supernatants) were measured. Results were compared with 31 longstanding T1D patients and ten healthy controls. RESULTS: Although HSP60 epitope-specific T-cell proliferative responses were detected, overall proliferative responses were low. At onset, epitope-specific intracellular IFN-γ production was higher in T1D patients compared with healthy controls (p < 0.05). At follow-up, both IL-10 and IFN-γ production were higher in those without a partial remission than in those with a partial remission (both p < 0.05). Also, IL-10 and IFN-γ production were higher compared with onset for patients without a PR (both p < 0.01). In supernatants of HSP60 epitope-specific T-cell cultures, no substantial differences in cytokine production were found between T1D patients with and without a partial remission, either at onset or a few months after onset. As patient numbers were small, results should be interpreted with caution. CONCLUSIONS: Pan-DR-binding HSP60 peptides induced low peptide-specific proliferative responses and peptide-specific production of some, mainly intracellular, cytokines in T1D patients. Recognition did not differ significantly between patient groups and various time points.

[Unilateral blindness following a non-surgical rhinoplasty with filler]. / Eenzijdige blindheid na een neuscorrectie met filler.

BACKGROUND: A rare but known adverse event following a cosmetic filler treatment is unilateral blindness. In the Netherlands, this complication has not been reported in a patient before. CASE DESCRIPTION: A 26-year-old woman developed unilateral blindness after undergoing a cosmetic treatment of the dorsum nasi in which hyaluronic acid was used as filler. The blindness was caused by backflow of the filler via the ophthalmic artery into the carotid internal artery. CONCLUSION: There is no proven effective treatment for this adverse event. Therefore prevention is of great importance. This requires knowledge of the anatomy of the facial blood vessels and a well-developed injection technique.

High production of 1,3-propanediol from industrial glycerol by a newly isolated Clostridium butyricum strain.

Batch and continuous cultures of a newly isolated Clostridium butyricum strain were carried out on industrial glycerol, the major by-product of the bio-diesel production process. For both types of cultures, the conversion yield obtained was around 0.55 g of 1,3-propanediol formed per 1 g of glycerol consumed whereas the highest 1,3-propanediol concentration, achieved during the single-stage continuous cultures was 35-48 g l-1. Moreover, the strain presented a strong tolerance at the inhibitory effect of the 1,3-propanediol, even at high concentrations of this substance at the chemostat (e.g. 80 g l-1). 1,3-Propanediol was associated with cell growth whereas acetate and butyrate seemed non growth-associated products. At low and medium dilution rates (until 0.1 h-1), butyrate production was favoured, whereas at higher rates acetate production increased. The maximum 1,3-propanediol volumetric productivity obtained was 5.5 g l-1 h-1. A two-stage continuous fermentation was also carried out. The first stage presented high 1,3-propanediol volumetric productivity, whereas the second stage (with a lower dilution rate) served to further increase the final product concentration. High 1,3-propanediol concentrations were achieved (41-46 g l-1), with a maximum volumetric productivity of 3.4 g l-1 h-1. A cell concentration decrease was reported between the second and the first fermentor.

Investigation of acetone-butanol-ethanol (ABE) fermentation by fluorescence.

Photophysical techniques have potential for the development of optical sensors in monitoring and controlling fermentors. In the particular case of acetone-butanol-ethanol (ABE) fermentation, carried out by bacteria of the speciesClostridium acetobutylicum, we have developed two studies based on fluorescence spectroscopy. First, we measured the intrinsic fluorescence of NADH related to bacteria metabolism, leading to a linear relationship between the NADH specific fluorescence and the specific rate of butyric acid production. At the same time, we have correlated enzymatic activities (acetate kinase, butyrate kinase, acetoacetate decarboxylase) with NADH specific fluorescence. Second, we studied the fluorescence polarization of extrinsic DPH (1,6-diphenyl-1,3,5-hexatriene) related to membrane fluidity. A simultaneous increase in both DPH anisotropy (order parameter increase) and butanol production is observed. Even though these results seem contradictory, because of the well-known fluidizing effect of butanol on lipids, they can be explained by a homeoviscous response ofC. acetobutylicum to the presence of butanol during fermentation. Thus the apparent changes in fluidity could be the result of the adaptative membrane alteration.