Insights into the lipoic acid metabolism in Staphylococcus aureus

DM RUIZ; D DE MENDOZA; MC MANSILLA

Medoza

Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Lipoic acid (LA) is a cofactor of several key enzymes involved in oxidative and single carbon metabolism. In the model gram-negative bacterium Escherichia coli, LipB transfers octanoate to target proteins and these octanoylated domains are converted into lipoylated derivatives by lipoyl synthase (LipA). Exogenous free LA can also be scavenged by the lipoyl ligase. However, in the gram-positive Bacillus subtilis two additional proteins are required: LipL and GcvH. Analysis of gram-positive pathogens genomes revealed that homologues to these genes can be found in most of them. The aim of this work was to study lipoylation mechanisms in S. aureus. The function of LA genes was inferred from genetic and physiological experiments. Although S. aureus encodes two lipoyl ligases homologs only one was able to functionally replace Bacillus subtilis LplJ. The expression of S. aureus octanoyltransferase (LipM) restored growth of the respective B. subtilis mutant. Besides, S. aureus lipM mutant was unable to grow in minimal medium and this deficiency was rescued by the addition of the products of LA-dependent enzymes, suggesting that LA biosynthesis pathway might be conserved among gram-positive pathogenic bacteria. The knowledge about LA metabolism in pathogens is of great relevance because it might be an excellent target for the development of new antimicrobials.