2003
DOI: 10.1126/science.1088170
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Listeria Intracellular Growth and Virulence Require Host-Derived Lipoic Acid

Abstract: Listeria monocytogenes is a Gram-positive intracytosolic pathogen that causes severe disease in pregnant and immunocompromised individuals. We found that L. monocytogenes lacking the lipoate protein ligase LplA1 was defective for growth specifically in the host cytosol and was less virulent in animals by a factor of 300. A major target for LplA1, the E2 subunit of pyruvate dehydrogenase (PDH), lacked a critical lipoyl modification when the DeltalplA1 strain was grown intracellularly, which suggests that aborti… Show more

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Cited by 142 publications
(128 citation statements)
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“…This finding is relevant because antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent (48), and several major classes of bactericidal antibiotics operate through the production of highly deleterious hydroxyl radicals in both Gram-negative and Gram-positive bacteria (49). Remarkably, lipoyl groups are essential for parasite survival in host cells (50,51) and for virulence (52). Indeed, the utilization of lipoylated proteins for Ohr reduction represents an emerging area of investigation (19) into the likelihood that specific proteins perform multiple catalytic functions to provide a means to regulate divergent processes, with a single molecular switch.…”
Section: Discussionmentioning
confidence: 99%
“…This finding is relevant because antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent (48), and several major classes of bactericidal antibiotics operate through the production of highly deleterious hydroxyl radicals in both Gram-negative and Gram-positive bacteria (49). Remarkably, lipoyl groups are essential for parasite survival in host cells (50,51) and for virulence (52). Indeed, the utilization of lipoylated proteins for Ohr reduction represents an emerging area of investigation (19) into the likelihood that specific proteins perform multiple catalytic functions to provide a means to regulate divergent processes, with a single molecular switch.…”
Section: Discussionmentioning
confidence: 99%
“…This is thought to be the principal route for generating free lipoate in metazoan animals which obtain their lipoic acid requirement from food and intestinal bacteria (55,56). Animal pathogens are also able to scavenge the free lipoate generated by host digestion (3,29,164). 206 SPALDING AND PRIGGE MICROBIOL.…”
Section: Lipoate Cleavagementioning
confidence: 99%
“…This enzyme is essential to perform a critical lipoyl modification in the E2 subunit of pyruvate dehydrogenase, in the presence of limiting concentrations of available host lipoyl substrates, which suggests that abortive growth is due to loss of pyruvate dehydrogenase function. 147,148 pycA encodes a pyruvate carboxylase, an enzyme of the tricarboxylic acid cycle. A pycA insertion mutant is unable to replicate in mammalian macrophages and epithelial cells.…”
Section: O N O T D I S T R I B U T Ementioning
confidence: 99%