Metabolic reprogramming in the food-borne pathogen Listeria monocytogenes as a critical defence against acid stress

The ability to sense and respond effectively to acidic stress is important for microorganisms to survive and proliferate in fluctuating environments. As specific metabolic activities can serve to buffer the cytoplasmic pH, microorganisms rewire their metabolism to favour these reactions and thereby mitigate acid stress. The orally acquired pathogen Listeria monocytogenes exploits alternative metabolic activities to overcome the acidic stress encountered in the human stomach or food products. In this minireview, we discuss the metabolic processes in L. monocytogenes that mitigate acid stress, with an emphasis on the proton-depleting reactions, including glutamate decarboxylation, arginine/agmatine deimination, and fermentative acetoin production. We also summarize the recent findings on regulatory mechanisms that control the expression of genes that are responsible for these metabolic activities, including the general stress response regulator SigB, arginine repressor ArgR, and the recently discovered RofA-like transcriptional regulatory GadR. We further discuss the importance of this metabolic reprogramming in the context of food products and within the host. Finally, we highlight some outstanding challenges in the field, including an understanding of acid-sensing mechanisms, the role of intraspecies heterogeneity in acid resistance, and how a fundamental understanding of acid stress response can be exploited for food formulation to improve food safety and reduce food waste.