Bacterial energy metabolism as potential anti-tuberculosis target

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It is a widespread opinion, especially in the western culture, that TB is a plague of the past, whose lethality was caused by poor living conditions and lack of antibiotics. On the contrary, in 2015 1.3 million TB related deaths occurred worldwide. In fact, TB is still the second most common infectious disease in terms of numbers of victims, outpaced only by AIDS. Currently the cure remains challenging, mainly because the standard drug therapy includes a cocktail of four drugs for a minimum period of six months. In case of multi-drug resistant or extensively drug resistant tuberculosis, chemotherapy needs to be expanded up to 2 years. So it is easy to picture the possibility of toxicity problems and the gradual loss of patient compliance. Therefore, it is necessary to find new targets and new drug combinations for shortening TB chemotherapy.

Ludovica Mascolo is studying the mycobacterial energy metabolism as potential antibiotic target. The bacterial energy metabolism, is a complex system formed by a series of proteins, with two key tasks: (I) convert food in energy through aerobic respiration (in presence of oxygen), and (II) protect bacteria from different kind of stress (including antibiotic treatment). Therefore,  energy metabolism can be considered as a possible antibiotic target.

More specifically, Mascolo and her colleagues intend to face the problem in 2 ways: (I) investigate the energy metabolism as potential target of known promising antibiotics and (II) screen compound libraries supplied by chemistry colleagues against energy metabolism, testing their effectiveness, toxicity and pharmacokinetics. Currently Mascolo is investigating the mechanism of action of a very promising class of anti-tubercular drug presently in a clinical trial. The research showed that these drugs clearly interfered with bacterial respiration in a time- and dose-dependent manner. Presently, she tries to link these results to bacterial killing and also started the screening of a library of potential energy metabolism inhibitors.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 713669.

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