Listeria monocytogenes cytosolic metabolism promotes replication, survival, and evasion of innate immunity

Abstract

Listeria monocytogenes, the causative agent of listeriosis, is an intracellular pathogen that is exquisitely evolved to survive and replicate in the cytosol of eukaryotic cells. Eukaryotic cells typically restrict bacteria from colonising the cytosol, likely through a combination of cell autonomous defences, nutritional immunity, and innate immune responses including induction of programmed cell death. This suggests that L. monocytogenes and other professional cytosolic pathogens possess unique metabolic adaptations, not only to support replication but also to facilitate resistance to host-derived stresses/defences and avoidance of innate immune activation. In this review, we outline our current understanding of L. monocytogenes metabolism in the host cytosol and highlight major metabolic processes which promote intracellular replication and survival.

Keywords: Listeria monocytogenes; cytosol; intracellular; metabolism; virulence.

Fig 1

Overview of select L. monocytogenes metabolic pathways that determine intracellular replication and survival. During colonization of host cells, L. monocytogenes transports host-derived metabolites through various nutrient transport systems. These metabolites are used by L. monocytogenes both for catabolic and anabolic pathways to replicate in the host cytosol and resist cytosolic stresses. Green text denotes L. monocytogenes enzymes crucial for intracellular replication and/or survival. Abbreviations: ETC - electron transport chain, DHNA - 1,4-dihydroxy-2-naphthoate, BKD - branched-chain α-keto acid dehydrogenase complex.