# Transcriptomic Analysis of Biofilm Formation Inhibition by PDIA Iminosugar in Staphylococcus aureus

## TL;DR

This study shows how a synthetic iminosugar called PDIA inhibits biofilm formation in Staphylococcus aureus by altering gene expression related to metabolism and cell structure.

## Contribution

The paper reveals novel insights into the transcriptomic effects of PDIA on S. aureus, particularly its impact on phage-related and cell wall genes.

## Key findings

- PDIA down-regulates bacteriophage genes involved in bacterial cell lysis and cell wall degradation.
- The phosphotransferase system (PTS) genes are among the most upregulated by PDIA exposure.
- PDIA affects genes involved in peptidoglycan synthesis and lysis after 24 hours of exposure.

## Abstract

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.