Luiz Pedro Sorio de Carvalho, Ph.D.

Diseases caused by bacteria from the genus Mycobacterium afflict humankind for millennia and currently represent a significant source of mortality and morbidity. Examples are human tuberculosis, leprosy, Buruli ulcer and other soft-tissue and lung infections. Tuberculosis alone is still responsible for 1.5 million deaths annually. The increased prevalence of antibiotic resistance in mycobacteria is a significant problem, causing nearly untreatable infections. The Carvalho group is interested in defining how soil-dwelling and water-born mycobacteria became adapted to the human host, a pre-requisite for a human pathogen. In particular, our group is focused on understanding how mycobacterial metabolism and chemistry evolved in the last 50 million years, to allow for optimal growth and virulence in humans. Once these processes have been mapped and characterized at cellular and molecular levels, we will employ state-of-the-art methods, some of which have been pioneered at UF Scripps, to discover and develop novel small molecules capable of killing these pathogens and transform the therapy of tuberculosis and other mycobacterial diseases.

Key recent advances include:

(i) discovery of the first example of target-mediated antibiotic inactivation

(ii) identification of the metabolic requirements for pyruvate and lactate utilization by M. tuberculosis

(iii) discovery of itaconate catabolism in M. tuberculosis and its intersection with amino acid metabolism

(iv) carried out the first fine mapping of nitrogen metabolism in M. tuberculosis.

(v) demonstration of the crucial role of metabolism in bacterial L-form

(vi) discovery of the first NAD+ phosphorylase and its role in M. tuberculosis cell death