title: Reporter metabolite analysis of transcriptional profiles of a Staphylococcus aureus strain with normal phenotype and its isogenic hemB mutant displaying the small-colony-variant phenotype.
abstract: In this study, full-genome DNA microarrays based on the sequence of Staphylococcus aureus N315 were used to compare the transcriptome of a clinical S. aureus strain with a normal phenotype to that of its isogenic mutant with a stable small-colony-variant (SCV) phenotype (hemB::ermB). In addition to standard statistical analyses, systems biology advances were applied to identify reporter metabolites and to achieve a more detailed survey of genome-wide expression differences between the hemB mutant and its parental strain. Genes of enzymes involved in glycolytic and fermentative pathways were found to be up-regulated in the hemB mutant. Furthermore, our analyses allowed identification of additional differences between the normal-phenotype S. aureus and the SCV, most of which were related to metabolism. Profound differences were identified especially in purine biosynthesis as well as in arginine and proline metabolism. Of particular interest, a hypothetical gene of the Crp/Fnr family (SA2424) that is part of the arginine-deiminase (AD) pathway, whose homologue in Streptococcus suis is assumed to be involved in intracellular persistence, showed significantly increased transcription in the hemB mutant. The hemB mutant potentially uses the up-regulated AD pathway to produce ATP or (through ammonia production) to counteract the acidic environment that prevails intracellularly. Moreover, genes involved in capsular polysaccharide and cell wall synthesis were found to be significantly up-regulated in the hemB mutant and therefore potentially responsible for the changed cell morphology of SCVs. In conclusion, the identified differences may be responsible for the SCV phenotype and its association with chronic and persistent infections.
authors.affiliation: Institute of Medical Microbiology, University Hospital of Münster, Domagkstrasse 10, 48149 Münster, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Seggewiss
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.forename: Oliver
authors.initials: O
authors.lastname: Kotte
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Mohammad Reza Khoschkhoi
authors.initials: MR
authors.lastname: Yazdi
authors.forename: Andreas
authors.initials: A
authors.lastname: Fischer
authors.forename: Peter
authors.initials: P
authors.lastname: McNamara
authors.forename: Nahed
authors.initials: N
authors.lastname: Al Laham
authors.forename: Richard
authors.initials: R
authors.lastname: Proctor
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.forename: Matthias
authors.initials: M
authors.lastname: Heinemann
authors.forename: Christof
authors.initials: C
authors.lastname: von Eiff
mesh_terms: D001120:Arginine / Q000378:metabolism; D016667:Bacterial Capsules / Q000737:chemistry / Q000235:genetics; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D005285:Fermentation; D020869:Gene Expression Profiling; D014644:Genetic Variation; D016680:Genome, Bacterial; D006019:Glycolysis; D006427:Hemin / Q000235:genetics; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011134:Polysaccharides / Q000096:biosynthesis / Q000235:genetics; D011392:Proline / Q000378:metabolism; D011687:Purines / Q000096:biosynthesis; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D011134:Polysaccharides; D011687:Purines; D006427:Hemin; D001120:Arginine; D011392:Proline; C030985:purine