Deciphering mechanisms of production of natural compounds using inducer-producer microbial consortia.

Living organisms produce a wide range of metabolites. Because of their potential antibacterial, antifungal, antiviral, or cytostatic properties, such natural molecules are of high interest to the pharmaceutical industry. In nature, these metabolites are often synthesized via secondary metabolic biosynthetic gene clusters that are silent under the typical culturing conditions. Among different techniques used to activate these silent gene clusters, co-culturing of "producer" species with specific "inducer" microbes is a particularly appealing approach due to its simplicity. Although several "inducer-producer" microbial consortia have been reported in the literature and hundreds of different secondary metabolites with attractive biopharmaceutical properties have been described as a result of co-cultivating inducer-producer consortia, less attention has been devoted to the understanding of the mechanisms and possible means of induction for production of secondary metabolites in co-cultures. This lack of understanding of fundamental biological functions and inter-species interactions significantly limits the diversity and yield of valuable compounds using biological engineering tools. In this review, we summarize and categorize the known physiological mechanisms of production of secondary metabolites in inducer-producer consortia, and then discuss approaches that could be exploited to optimize the discovery and production of secondary metabolites.

In Vivo Study of Osteochondral Defect Regeneration Using Innovative Composite Calcium Phosphate Biocement in a Sheep Model.

This study aimed to clarify the therapeutic effect and regenerative potential of the novel, amino acids-enriched acellular biocement (CAL) based on calcium phosphate on osteochondral defects in sheep. Eighteen sheep were divided into three groups, the treated group (osteochondral defects filled with a CAL biomaterial), the treated group with a biocement without amino acids (C cement), and the untreated group (spontaneous healing). Cartilages of all three groups were compared with natural cartilage (negative control). After six months, sheep were evaluated by gross appearance, histological staining, immunohistochemical staining, histological scores, X-ray, micro-CT, and MRI. Treatment of osteochondral defects by CAL resulted in efficient articular cartilage regeneration, with a predominant structural and histological characteristic of hyaline cartilage, contrary to fibrocartilage, fibrous tissue or disordered mixed tissue on untreated defect (p < 0.001, modified O'Driscoll score). MRI results of treated defects showed well-integrated and regenerated cartilage with similar signal intensity, regularity of the articular surface, and cartilage thickness with respect to adjacent native cartilage. We have demonstrated that the use of new biocement represents an effective solution for the successful treatment of osteochondral defects in a sheep animal model, can induce an endogenous regeneration of cartilage in situ, and provides several benefits for the design of future therapies supporting osteochondral defect healing.