Research Interest

Two main lines of research are actually pursuing:

1)         Identification of targets for new drugs in Mycobacterium tuberculosis

Tuberculosis (TB) remains the leading cause of mortality due to a bacterial pathogen, Mycobacterium tuberculosis. Moreover, M. tuberculosis strains that are resistant to an increasing number of second-line drugs used to treat multidrug-resistant tuberculosis (MDR-TB, XDR-TB, and TDR-TB) are becoming a threat to public health worldwide. Consequently, there is an urgent necessity of new TB drugs. More precisely, our laboratory is aimed to find the target and the mechanism of action of new drugs.

Within the EC-VI framework cluster “New Medicines for Tuberculosis” we have identified the target of a new drug, belonging to the class of benzothiazinones, whose antitubercular activity has been well demonstrated in vitro, ex vivo, and in a mouse model of TB. The drug is now in preclinical-test. The achieved results have been published in SCIENCE and the article has been cited as one of the "key papers" published in 2009 (see: Nature Medicines 15: 1349).

The target has been patented (US 2011/0262361 A1) and the license sold to an International Pharmaceutical Company (http://www.sentinel.it/uk/).

Recently, the new cluster “More Medicines for Tuberculosis” has been funded by EC-VII framework (2011-2015) and is aimed to find new and more antituberculardrugs. The Applicant is part of the Steering Committee.

2)         Deciphering the role of RND efflux transporters in Burkholderia cenocepacia

Burkholderiacenocepacia J2315 is representative of a highly problematic group of cystic fibrosis (CF) pathogens with the antimicrobial therapy being ineffective due to its high resistance to clinically relevant antimicrobial agents. RND (Resistance-Nodulation-Cell Division) efflux pumps are known to be among the mediators of multidrug resistance in Gram-negative bacteria. Since the significance of the 16 RND efflux systems present in B. cenocepacia (named RND-1 to -16) was only partially determined, the aim of our work was to analyze mutants of B. cenocepacia strain J2315 impaired in RND efflux systems, and assess their role in the efflux of toxic compounds. The data revealed that RND-4 made a significant contribution to the antibiotic resistance of B. cenocepacia. Moreover, transcriptome analysis of mutants deleted in RND-4 showed that motility and chemotaxis-related genes appeared to be up-regulated in this strain.