Seminar by Dr. Francesco Musiani

University of Bologna, Bologna (ITALY)

A computational approach to nickel trafficking and utilization in pathogenic bacteria

Nickel is a virulence determinant for several human pathogens. Most of them possesses two nickel-dependent enzymes that are essential for their life cycle: [Ni,Fe]-hydrogenase and urease. The survival of such bacteria relies on an important supply of nickel, implying a tight control of its import, distribution, storage and export. Here I will focus on some computational results on the pathways of activation of the nickel enzymes as well as on nickel uptake, trafficking and on the regulation of nickel dependent proteins. These include (i) an inner-membrane nickel uptake system, the NiuBDE ATP-dependent transporter, (ii) proteins involved in nickel trafficking and distribution between urease and hydrogenase (UreE and HypA) and, (iii) nickel-dependent transcriptional regulators (NikR, RcnR and InrS), and (iv) urease accessory proteins and nickel trafficking through proteins tunnels (UreD, UreF and UreG). Taken together, these proteins offer a wide choice of novel therapeutic targets that can be used for the treatment against the infection of several antibiotic-resistant bacteria.