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Photo of Prof. Carvalho. He's wearing a blue shirt.

Biochemistry Seminar of Special Interest: Dr. Luiz Pedro Carvalho (The Francis Crick Institute), "Allosteric activation of metabolic pathways as an innovative antibiotic strategy"

Event Type
Dr. Satish Nair
Feb 18, 2022   12:00 pm  
Prof. Luiz Pedro Carvalho
Cara Day
Originating Calendar
Biochemistry Department Seminars

We have entered the “antibiotic apocalypse” era, where formerly treatable bacterial infections are now incurable, leading to significant morbidity and mortality worldwide. The scientific community is responsible for bringing in innovative ideas that might catalyse the discovery of novel treatments. On novelty, all antibiotics in clinical use act in the same way, that is, they are inhibitors of important cellular processes. For example, rifamycins inhibit RNA polymerase, aminoglycosides inhibit protein synthesis, and β-lactam antibiotics inhibit the assembly of peptidoglycan. In this seminar, I will explore a new concept. We propose that activation of metabolic pathways can also be harnessed to interfere with bacterial growth and kill bacteria. To demonstrate the potential of this approach, we explore proof-of-concept activation of L-histidine biosynthesis in Mycobacterium tuberculosis. We take a biochemical and genetic approach to establish that artificial over-activation of this pathway is detrimental to M. tuberculosis in vitro and in mice. These results pave the way for a new therapeutic modality, where bacterial cells will be forced to over-produce certain metabolites, leading to depletion of essential nutrients, energy imbalance and potentially toxic effects.

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