%0 Journal Article
%T Living with an imperfect cell wall: compensation of femAB inactivation in Staphylococcus aureus
%A Judith H¨¹bscher
%A Andrea Jansen
%A Oliver Kotte
%A Juliane Sch£¿fer
%A Paul A Majcherczyk
%A Llinos G Harris
%A Gabriele Bierbaum
%A Matthias Heinemann
%A Brigitte Berger-B£¿chi
%J BMC Genomics
%D 2007
%I BioMed Central
%R 10.1186/1471-2164-8-307
%X In addition to slow growth, the cis-complemented femAB mutant showed temperature sensitivity and a higher methicillin resistance than the wild type. Transcriptional profiling paired with reporter metabolite analysis revealed multiple changes in the global transcriptome. A number of transporters for sugars, glycerol, and glycine betaine, some of which could serve as osmoprotectants, were upregulated. Striking differences were found in the transcription of several genes involved in nitrogen metabolism and the arginine-deiminase pathway, an alternative for ATP production. In addition, microarray data indicated enhanced expression of virulence factors that correlated with premature expression of the global regulators sae, sarA, and agr.Survival under conditions preventing normal cell wall formation triggered complex adaptations that incurred a fitness cost, showing the remarkable flexibility of S. aureus to circumvent cell wall damage. Potential FemAB inhibitors would have to be used in combination with other antibiotics to prevent selection of resistant survivors.The peptidoglycan structure of Staphylococcus aureus is a dynamic, three-dimensional meshwork consisting of multiple layers of glycan strands that are crosslinked through peptide bridges. It determines the bacterial shape and confers protection against the high internal turgor. Characteristic for the staphylococcal peptidoglycan is the long and flexible pentaglycine interpeptide, which branches off the ¦Å-amino group of the L-lysine of the peptidoglycan stem peptide. The pentaglycine interpeptide is synthesized in a sequential fashion by the FemABX family of nonribosomal peptidyl transferases, which use glycyl-tRNA as a glycine donor. While FemX (synonym: FmhB) adds the first glycine, FemA and FemB add Gly2,3 and Gly4,5, respectively [1-4]. Although structurally and functionally related, these factors cannot substitute for one another [5]. Growth of mutants with a shortened interpeptide is strongly impaired [2]
%U http://www.biomedcentral.com/1471-2164/8/307