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Dr. Luiz de Carvalho - Learning metabolic lessons from the best tutor, Mycobacterium tuberculosis

Luiz P. de Carvalho

The Francis Crick Institute, London, UK

Learning metabolic lessons from the best tutor, Mycobacterium tuberculosis

Since the landmark publication of the genome of Mycobacterium tuberculosis in the late 90s’s, we have seen a significant increase in our understanding of M. tuberculosis metabolism. These recent findings often challenge textbook knowledge derived from studies with model bacteria. During this seminar I will illustrate key examples of these step-changes in our knowledge and how they were achieved. These include the discovery of enzymes and entire metabolic pathways, which were initially refractory to annotation. Also, we will highlight unique aspects of M. tuberculosis physiology that cannot be appreciated from genomics, transcriptomics and proteomics experiments. We will cover pathways involved in core metabolism, as well as plasma membrane and cell envelope remodelling.

Selected publications

  • de Chiara C, Homšak M, Prosser GA, Douglas HL, Garza-Garcia A, Kelly G, Purkiss AG, Tate EW, de Carvalho LPS. D-Cycloserine destruction by alanine racemase and the limit of irreversible inhibition. Nat Chem Biol. 2020 16(6):686-694
  • Evangelopoulos D, Prosser GA, Rodgers A, Dagg BM, Khatri B, Ho MM, Gutierrez MG, Cortes T, de Carvalho LPS. Comparative fitness analysis of D-cycloserine resistant mutants reveals both fitness-neutral and high-fitness cost genotypes. Nat Commun. 2019 10(1):4177
  • Serafini A, Tan L, Horswell S, Howell S, Greenwood DJ, Hunt DM, Phan MD, Schembri M, Monteleone M, Montague CR, Britton W, Garza-Garcia A, Snijders AP, VanderVen B, Gutierrez MG, West NP, de Carvalho LPS. Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism. Mol Microbiol. 2019 112(4):1284-1307
  • Wang H, Fedorov AA, Fedorov EV, Hunt DM, Rodgers A, Douglas HL, Garza-Garcia A, Bonanno JB, Almo SC, de Carvalho LPS. An essential bifunctional enzyme in Mycobacterium tuberculosis for itaconate dissimilation and leucine catabolism. Proc Natl Acad Sci USA. 2019 116(32):15907-15913
  • Agapova A, Serafini A, Petridis M, Hunt DM, Garza-Garcia A, Sohaskey CD, de Carvalho LPS. Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis. Elife. 2019 8:e41129
  • Larrouy-Maumus G, Marino LB, Madduri AV, Ragan TJ, Hunt DM, Bassano L, Gutierrez MG, Moody DB, Pavan FR, de Carvalho LP. Cell-Envelope Remodeling as a Determinant of Phenotypic Antibacterial Tolerance in Mycobacterium tuberculosis. ACS Infect Dis. 2016 2(5):352-360
  • Ganapathy U, Marrero J, Calhoun S, Eoh H, de Carvalho LPS, Rhee K, Ehrt S. Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis. Nat Commun. 2015 6:7912
  • Larrouy-Maumus G, Biswas T, Hunt DM, Kelly G, Tsodikov OV, de Carvalho LP. Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 2013 110(28):11320-5



Contact: Jérome Nigou (

Link to attend the seminar :

2 Feb

11:00 - 12:00

Online seminar