Many difficult-to-treat human infections related to catheters and other indwelling devices are caused by bacteria residing in biofilms. One of the key properties of microorganisms residing in a biofilm is decreased susceptibility towards antimicrobial agents. Therefore, many different approaches have been researched to destroy or inhibit biofilm production by bacteria. Different iminosugars (IS) were reported to inhibit biofilm formation in S. mutans, S. aureus, and P. aeruginosa. The aim of this study was to look for a spectrum of the activity in one of these IS. The iminosugar PDIA beta-1-C-propyl-1,4-dideoxy-1,4-imino-L-arabinitol was tested in vitro at the same concentration against 30 different strains of the most important Gram-negative and Gram-positive human pathogens looking for their biofilm production and viability at different time intervals. It appeared that PDIA inhibited biofilm production of Enterobacter spp., P. aeruginosa, Enterococcus spp. and S. aureus in 8 h, and Klebsiella spp., Acinetobacter spp. and S.epidermidis in 24 h. PDIA caused no growth inhibition of the tested bacteria at a concentration of 0.9 mM. Our results indicate a broad-spectrum biofilm inhibitory activity of PDIA. which may be the basis for future application studies that will help in control of the associated device and biofilm-related infections caused by a wide spectrum of the causative agents.

A concise, stereocontrolled synthesis of the aminocyclopentenediol component of queuosine from l -ribose by way of a N-t -butanesulfinyl glycosylamine is reported.

Background: Iminosugars are natural or synthetic sugar analogues with a very broad spectrum of activities, including those against the 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 (beta-1-C-propyl-1,4-dideoxy-1,4-imino-L-arabinitol), possesses the ability to suppress biofilm production by different pathogenic bacteria without inhibiting their growth. Thereby, PDIA is able to influence experimental 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 h in comparison to a control without the iminosugar. The RNA was then isolated, converted into cDNA, sequenced, and data analysis was performed. Results: It appeared that PDIA caused the 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 system (PTS), which is required for carbohydrate uptake and control of carbon metabolism. The ranking of the most significant down-regulated genes after 24 h exposure to PDIA shows that they predominantly coded for both the synthesis and lysis of the peptidoglycan. Conclusions: We have shown here that the influence of PDIA on the expression of S. aureus genes is broad and affects many genes encoding metabolism and ribosomes.

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.