Inactivation of Fructose-1,6-Bisphosphate Aldolase Prevents Optimal Co-catabolism of Glycolytic and Gluconeogenic Carbon Substrates in

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The development of new chemotherapies targeting Mycobacterium tuberculosis (Mtb) will benefit from genetic evaluation of potential drug targets and a better understanding of the pathways required by Mtb to establish and maintain chronic infections. We employed a genetic approach to investigate the essentiality of fructose-1,6-bisphosphate aldolase (FBA) for growth and survival of Mtb in vitro and in mice. A conditional fba mutant revealed that Mtb requires FBA for growth in the acute phase and for survival in the chronic phase of mouse infections. In vitro essentiality of fba was strictly condition-dependent. An FBA deletion mutant (Δfba) required a balanced combination of carbon substrates entering metabolism above and below the FBA-catalyzed reaction for growth and died in media with single carbon sources and in mouse lungs. Death of Δfba in vitro was associated with the perturbation of intracellular metabolites. These studies highlight how a conditional fba mutant helped identify conditions in which FBA is dispensable for growth of Mtb, evaluate FBA as a potential target for eliminating persistent bacilli and offer insight into metabolic regulation of carbon co-catabolism in Mtb.

Vyšlo v časopise: Inactivation of Fructose-1,6-Bisphosphate Aldolase Prevents Optimal Co-catabolism of Glycolytic and Gluconeogenic Carbon Substrates in. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004144
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004144

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