Maleic Acid Enhances Acid Sensitivity of Listeria monocytogenes through Inhibition of the Glutamate Decarboxylase Activity

Introduction: Listeria monocytogenes is the most deadly foodborne pathogen, causing listeriosis which is responsible for most deaths from food poisoning than any other pathogen. The Glutamate Decarboxylase (GAD) system is the most important mechanism of acid resistance in L. monocytogenes allowing it to survive in acidic foods or pass through the stomach. 

Purpose: To investigate the effect of various compounds on the GAD system activity and acid resistance of L. monocytogenes

Methods: The Minimum Inhibitory Concentrations of various compounds on L. monocytogenes strains 10403S and EGD-e were identified and subsequently, their role in survival under lethal acidic conditions (pH 3, HCl) and on GAD activity was assessed with the use of mutants in GAD decarboxylase genes (stationary phase, BHI, 37^oC). Extracellular γ-amino butyric acid (GABAe) and intracellular γ-amino butyric acid (GABAi) was studied in all strains and mutants in the presence or absence of all compounds, under sublethal acidic conditions to assess the effect of the compounds in the activity of each decarboxylase. Furthermore, the effect of these compounds on the GAD activity in protein lysates was investigated. Finally, it was assessed the ability of each of the compounds to remove and/or inhibit biofilms formation

Results: Out of dozens of compounds, maleic acid was able to increase the acid sensitivity of both 10403S WT and EGD-e. GadD1 did not play any role in acid resistance while GadD3 played a role but was not affected by maleic acid. GadD2 was the major determinant of GAD activity and its activity was inhibited in the presence of maleic acid as was also shown in protein lysates.

Significance: Maleic acid can significantly modulate the acid resistance of L. monocytogenes through the inhibition of GAD activity and used in disinfection regimes to eliminate this pathogen from foods and lower the incidence of disease.