Transcriptomic Analysis of Biofilm Formation Inhibition by Pdia Iminosugar in <em>Staphylococcus aureus</em>

Background: Iminosugars are natural or synthetic sugar analogues with a very broad spectrum of activities including these against most prominent bacterial pathogens like P. aeruginosa or S. aureus. In a series of studies, we have demonstrated that one of the synthetic iminosugars, PDIA (be-ta-1-C-propyl-1,4-dideoxy-1,4-imino-L-arabinitol) possesses ability to suppress biofilm production by dif-ferent pathogenic bacteria without inhibiting their growth and on this way PDIA is able to influence experi-mental skin infection caused by S. aureus. Methods: To elucidate molecular mechanisms by which PDIA impedes biofilm formation by S. aureus, a transcriptomic study was performed in which a biofilm producing S. aureus strain was grown in the presence of PDIA for 24 and 48 hours in comparison to control without the iminosugar. The RNA was then isolated, converted into cDNA, sequenced and data analysis performed. Results: It appeared that PDIA caused down-regulation of many bacteriophage genes responsible for the processes of bacterial cell lysis, and some genes responsible for cell wall degradation were also down-regulated. Among the 25 most upregulated genes were those representing the phosphotransferase sys-tem (PTS), which is required for carbohydrate uptake and control of carbon metabolism. The ranking of the most significant down-regulated genes after 24-hour exposure to PDIA shows that they predominantly coded for both synthesis and lysis of the peptidoglycan. Conclusions: We have shown here that the influ-ence of PDIA on the expression of S. aureus genes is broad and affects many genes encoding metabolism and ribosomes.