Abstract
The enzyme fructose-bisphosphate aldolase occupies a central position in glycolysis and gluconeogenesis pathways. Beyond its housekeeping role in metabolism, fructose-bisphosphate aldolase has been involved in additional functions and is considered as a potential target for drug development against pathogenic bacteria. Here, we address the role of fructose-bisphosphate aldolase in the bacterial pathogen Francisella novicida. We demonstrate that fructose-bisphosphate aldolase is important for bacterial multiplication in macrophages in the presence of gluconeogenic substrates. In addition, we unravel a direct role of this metabolic enzyme in transcription regulation of genes katG and rpoA, encoding catalase and an RNA polymerase subunit, respectively. We propose a model in which fructose-bisphosphate aldolase participates in the control of host redox homeostasis and the inflammatory immune response.
Highlights
The enzyme fructose-bisphosphate aldolase occupies a central position in glycolysis and gluconeogenesis pathways
To assess the impact of bacterial infection and multiplication on the metabolism of infected macrophages, we first analyzed the metabolome of mouse bone marrow-derived macrophages (BMMs) and compared the concentration of a series of metabolites recorded in non-infected (NI) cells to those recorded in infected cells
We used for infection, either wild-type (WT) F. novicida (WT) or a F. novicida mutant with a deletion of the entire Francisella pathogenicity Island
Summary
The enzyme fructose-bisphosphate aldolase occupies a central position in glycolysis and gluconeogenesis pathways. We address the role of fructose-bisphosphate aldolase in the bacterial pathogen Francisella novicida. We decided to address the role of the unique class II fructose-1,6-bisphosphate aldolase (FBA) of Francisella, a ubiquitous metabolic enzyme occupying a central position in glycolysis and gluconeogenesis pathways. Two different classes of FBAs, with different catalytic mechanisms, have been described according to their amino acid sequences and designated Class I- and Class-II FBAs, respectively[18,19,20] These aldolases have been implicated in many “moonlighting” or non-catalytic functions, based upon their binding affinity for multiple other proteins, in both prokaryotic and eukaryotic organisms[21]. Type A enzymes have been found mostly involved in glycolysis and gluconeogenesis, while diverse metabolic roles and substrate specificities have been reported for type B aldolases[21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
