Lipoic Acid Metabolism in Microbial Pathogens

Abstract

SUMMARY Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.

Peroxide Stimulon and Role of PerR in Group A Streptococcus

“…3G). While several genes in this locus are genes encoding hypothetical proteins, SPy1214 encodes a predicted lipoateprotein ligase (lplA) that uses exogenous lipoic acid to lipoylate components of keto acid dehydrogenase complexes (20,47,61), such as the E2 subunits of pyruvate dehydrogenase and protein H of the glycine cleavage system, with protein H encoded by SPy1217 (gcvH) in the same operon. Lipoic acid (6,8-thiooctanoic acid), a disulfide-containing cofactor, is essential for the decarboxylation activity of these complexes (61), but it has also been reported to contribute to bacterial defenses against oxidative stress (8).…”

Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins

“…1, C-H). Interestingly, a specific mammalian delipoylase has not been identified (24). Here, SIRT2, and to a lesser extent, SIRT1, SIRT3, and SIRT4 were able to hydrolyze the removal of the lipoyl group from lysine (Fig.…”

Chlamydia trachomatisSerovar L2 Can Utilize Exogenous Lipoic Acid through the Action of the Lipoic Acid Ligase LplA1

“…Although lipoic acid is a vital cofactor, details regarding its utilization by intracellular pathogens have started to emerge only recently (2,10,14,24,41). The obligate intracellular bacterium, C. trachomatis serovar L2, encodes for four proteins that are predicted to undergo lipoylation.…”