Tuberculosis (TB) is still the leading global cause of death from an infectious bacterial agent. Limiting tuberculosis epidemic spread is therefore an urgent global public health priority. As stated by the WHO, to stop the spread of the disease we need a new vaccine, with better coverage than the current Mycobacterium bovis BCG vaccine. This vaccine was first used in 1921 and, since then, there are still no new licensed tuberculosis vaccines. However, there is extremely active research in the field, with a steep acceleration in the past decades, due to the advance of technologies and more rational vaccine design strategies. This review aims to gather latest updates in vaccine development in the various clinical phases and to underline the contribution of Structural Vaccinology (SV) to the development of safer and effective antigens. In particular, SV and the development of vaccine adjuvants is making the use of subunit vaccines, which are the safest albeit the less antigenic ones, an achievable goal. Indeed, subunit vaccines overcome safety concerns but need to be rationally re-engineered to enhance their immunostimulating effects. The larger availability of antigen structural information as well as a better understanding of the complex host immune response to TB infection is a strong premise for a further acceleration of TB vaccine development.

Enzymatic conversion of polysaccharides in the lignocellulosic biomass is currently the subject of intensive research and will be a key technology in future biorefineries. Using a bioinformatics approach, we previously identified a putative endo-β-1,4-glucanase (DtCel5A) from Dictyoglomus thermophilum, a chemoorganotrophic and thermophilic bacterium. Here, we structurally and functionally characterize DtCel5A and show that it is endowed with remarkable thermal and chemical stability. The structural features of DtCel5A and of its complex with cellobiose have been investigated by combining X-ray crystallography and other biophysical studies. Importantly, biochemical assays show that DtCel5A retains its activity on cellulose at high temperatures and at elevated salt concentrations. These features make DtCel5A an enzyme with interesting biotechnological applications for biomass degradation.