Virulence Factors That Modulate the Cell Biology of Listeria Infection and the Host Response
ABSTRACT The Gram-positive bacterial pathogen Listeria monocytogenes has become one of the best studied models in infection biology. This review will update our knowledge of Listeria virulence factors and highlight their role during the Listeria infection process.
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ABSTRACT: Intracellular bacterial pathogens (IBPs) are dependent on various nutrients provided by the host cells. Different strategies may therefore be necessary to adapt the intracellular metabolism of IBPs to the host cells. The specific carbon sources, the catabolic pathways participating in their degradation, and the biosynthetic performances of IBPs are still poorly understood. In this report, we have exploited the technique of (13)C-isotopologue profiling to further study the carbon metabolism of Listeria monocytogenes by using the EGDe wild-type strain and mutants (defective in the uptake and/or catabolism of various carbon compounds) replicating in J774A.1 macrophages. For this goal, the infected macrophages were cultivated in the presence of [1,2-(13)C2]glucose, [U-(13)C3]glycerol, [U-(13)C3]pyruvate, [U-(13)C3]lactate, or a mix of [U-(13)C]amino acids. GC/MS-based isotopologue profiling showed efficient utilization of amino acids, glucose 6-phosphate, glycerol, and (at a low extent) also of lactate but not of pyruvate by the IBPs. Most amino acids imported from the host cells were directly used for bacterial protein biosynthesis and hardly catabolized. However, Asp was de novo synthesized by the IBPs and not imported from the host cell. As expected, glycerol was catabolized via the ATP-generating lower part of the glycolytic pathway, but apparently not used for gluconeogenesis. The intermediates generated from glucose 6-phosphate in the upper part of the glycolytic pathway and the pentose phosphate shunt likely serve primarily for anabolic purposes (probably for the biosynthesis of cell wall components and nucleotides). This bipartite bacterial metabolism which involves at least two major carbon substrates-glycerol mainly for energy supply and glucose 6-phosphate mainly for indispensible anabolic performances-may put less nutritional stress on the infected host cells, thereby extending the lifespan of the host cells to the benefit of the IBPs.Frontiers in Cellular and Infection Microbiology 11/2014; 4:156. DOI:10.3389/fcimb.2014.00156 · 2.62 Impact Factor
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ABSTRACT: Listeria monocytogenes is responsible for one of the most life-threatening food-borne infections and the leading cause of food-poisoning associated deaths in the UK. Infection may be of the unborn/newly born infant where disease may manifest as listeric abortion, stillbirth or late-onset neonatal listeriosis, while in adults, infection usually affects the central nervous system causing meningitis. Crucial to the survival of L. monocytogenes, both inside and outside the host, is its ability to acquire metals which act as cofactors for a broad range of its cellular proteins. However, L. monocytogenes must also protect itself against the innate toxicity of metals. The importance of metals in host-pathogen interactions is illustrated by the restriction of metals (including zinc and iron) in vertebrates in response to infection and the use of high levels of metals (copper and zinc) as part of the antimicrobial defences within host phagocytes. As such, L. monocytogenes is equipped with various mechanisms to tightly control its cellular metal pools and avoid metal poisoning. These include multiple DNA-binding metal-responsive transcription factors, metal-acquisition, metal-detoxification and metal-storage systems, some of which represent key L. monocytogenes virulence determinants. This review discusses current knowledge of the role of metals in L. monocytogenes infections, with a focus on the mechanisms that contribute to zinc and copper homeostasis in this organism. The requirement to precisely control cellular metal levels may impose a vulnerability to L. monocytogenes which can be exploited in antimicrobials and therapeutics. © 2014 Elsevier Ltd All rights reserved.Advances in Microbial Physiology 01/2014; 65:83-123. DOI:10.1016/bs.ampbs.2014.08.003 · 5.80 Impact Factor