P48

At onset of infection, host triggers nutritional immunity to contrast pathogen replication. The nutritional immunity consists in the variation of metal availability, whose distribution changes to starve or intoxicate pathogens. The latter have developed high affinity metal-binding molecules and efficient efflux pumps to defend themselves from these attacks. A poorly characterised aspect of bacterial physiology is the effect of variations of metal availability, reduced or excessive, on the carbon and nitrogen metabolism. We investigate the effects of Fe³⁺ starvation and wide range Mn²⁺ concentrations on Mycobacterium tuberculosis and Mycobacterium abscessus (Mab) physiology. We observed that i) Fe³⁺ starvation alters the bioenergetics of mycobacterial cells, which contrast this unbalance re-modelling the central metabolism; ii) Mab shows distinct growth phenotypes on the base of the carbon source provided; iii) mycobacteria have adapted to grow in a wide range of Mn²⁺ concentrations (from 0 to 800 mM). This last result appears particularly interesting considering that mycobacteria are routinely grown in media that contain less than 1 µM of Mn²⁺ or even no source of this metal, suggesting the possibility that several mycobacterial activities can be masked in such media. On the base of these observations, we compared the proteomes of Mab grown in the presence of low and high concentration of Mn²⁺, and in the presence of two alternative carbon sources, acetate and glucose, within the scope to identify metal- and/or carbon source-dependent differential expression of proteins and unmask potential new mechanisms.