Neisseria gonorrhoeae, the bacterium responsible for gonorrhea, is notorious for its resilience under difficult conditions. To survive in the nutrient-limited environment of the human host, Neisseria gonorrhoeae carefully regulates its use of proteins across metabolic pathways. The study “Optimal Protein Allocation Controls the Inhibition of GltA and AcnB in Neisseria gonorrhoeae” in Pathogens and Disease explores the precise management of protein resources under resource-constrained conditions, as explained in this #FEMSmicroBlog by Nabia Shahreen. #FascinatingMicrobes
A unique adaptation: Protein constraints shape metabolic behavior
To grow in the nutrient-restricted environment of the human body, Neisseria gonorrhoeae adapts the activities of its metabolic proteins. Having the entire gene set for a complete tricarboxylic acid cycle, Neisseria gonorrhoeae selectively limits the activity of two key enzymes: citrate synthase and aconitase.
As these two enzymes require high protein demands, their selective inhibition helps Neisseria gonorrhoeae to conserve protein. By prioritizing pathways that provide energy with minimal protein cost, Neisseria gonorrhoeae optimizes its metabolism to thrive under protein-limited conditions.
The study “Optimal Protein Allocation Controls the Inhibition of GltA and AcnB in Neisseria gonorrhoeae” in Pathogens and Disease found upon limitation of citrate synthase and aconitase, Neisseria gonorrhoeae shifts towards acetate overflow—a metabolic pathway that is often perceived as inefficient.
The study relied on a protein-constrained genome-scale metabolic model of Neisseria gonorrhoeae. This model integrates information on protein cost—such as enzyme turnover rates and molecular weights—into a genome-scale model. The simulation mimics the real-life limitations within the host. Protein limitations impact metabolic pathways resulting in Neisseria gonorrhoeae allocating its limited protein resources across various pathways.
Acetate overflow to conserve protein and energy
Upon varying protein availabilities, the model simulated shifts in energy-generating pathways. When protein availability was low, the model showed decreased flux through the tricarboxylic acid cycle. The block mainly occurred in reactions catalyzed by citrate synthase and aconitase.
These protein-intensive enzymes became bottlenecks in the tricarboxylic acid cycle, resulting in a potential shift towards acetate overflow metabolism. Many organisms use acetate overflow as a metabolic strategy to produce acetate instead of fully oxidizing glucose to carbon dioxide.
Since this strategy allows the cell to generate energy more rapidly and with less protein investment, it doesn’t maximize ATP yield – a seemingly wasteful strategy. But for Neisseria gonorrhoeae, this approach is beneficial. The acetate metabolic branch requires fewer proteins than the full tricarboxylic acid cycle, enabling it to conserve its protein and energy resources.
New potential strategies to treat bacterial pathogens
Additionally, the work highlights cysteine uptake as a potential weak point in Neisseria gonorrhoeae’s survival. The pathogen’s growth depends heavily on cysteine, and when deprived of this key amino acid, it struggles to survive. Hence, targeting cysteine transport or limiting its availability could open new strategies for treating Neisseria gonorrhoeae infections.
This study uncovered such vulnerabilities with potential for exciting therapeutic application. By disrupting critical metabolic pathways, we may have found possible approaches to prevent Neisseria gonorrhoeae from adapting to difficult environmental conditions.
- Read the article “Optimal Protein Allocation Controls the Inhibition of GltA and AcnB in Neisseria gonorrhoea” by Sharheen et al. in Pathogens and Diseases (2024).
Nabia Shahreen is a PhD student at the University of Nebraska-Lincoln, where she investigates the metabolic adaptations of antibiotic-resistant bacteria. Her work combines computational modeling with experimental insights to unravel how pathogens like Neisseria gonorrhoeae adopt specific metabolic strategies and how these contribute to their survival. With a background in engineering, Nabia enjoys bridging disciplines to solve biological mysteries.
About this blog section
The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.
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