Staphylococcus aureus treated with fosfomycin. Staphylococcus aureus

Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 µg/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes. Using meta-analysis of our results and the results in the S. aureus microarray database, we have confirmed that fosfomycin induces “cell wall stimulon” genes and were able to identify genes and pathways specifically modulated by fosfomycin. Overall design: Time course, different fosfomycin concentration