Inhibition of Biofilm Formation, Quorum Sensing and Infection in Pseudomonas aeruginosa by Natural Products-Inspired Organosulfur Compounds

Abstract

Using a microplate-based screening assay, the effects on Pseudomonas aeruginosa PAO1 biofilm formation of several S-substituted cysteine sulfoxides and their corresponding disulfide derivatives were evaluated. From our library of compounds, S-phenyl-L-cysteine sulfoxide and its breakdown product, diphenyl disulfide, significantly reduced the amount of biofilm formation by P. aeruginosa at levels equivalent to the active concentration of 4-nitropyridine-N-oxide (NPO) (1 mM). Unlike NPO, which is an established inhibitor of bacterial biofilms, our active compounds did not reduce planktonic cell growth and only affected biofilm formation. When used in a Drosophila-based infection model, both S-phenyl-L-cysteine sulfoxide and diphenyl disulfide significantly reduced the P. aeruginosa recovered 18 h post infection (relative to the control), and were non-lethal to the fly hosts. The possibility that the observed biofilm inhibitory effects were related to quorum sensing inhibition (QSI) was investigated using Escherichia coli-based reporters expressing P. aeruginosa lasR or rhIR response proteins, as well as an endogenous P. aeruginosa reporter from the lasI/lasR QS system. Inhibition of quorum sensing by S-phenyl-L-cysteine sulfoxide was observed in all of the reporter systems tested, whereas diphenyl disulfide did not exhibit QSI in either of the E. coli reporters, and showed very limited inhibition in the P. aeruginosa reporter. Since both compounds inhibit biofilm formation but do not show similar QSI activity, it is concluded that they may be functioning by different pathways. The hypothesis that biofilm inhibition by the two active compounds discovered in this work occurs through QSI is discussed.

Microbial contamination and biofilms on machines of metal industry using metalworking fluids with or without biocides

“…According to the previously reported results (Zhao and Liu, 2010;Cady et al 2012;Trafny et al 2013), the amount of the colorimetric product in the MTT assay is proportionally related to the size of microbial population growing in biofilms. The crystal violet assay usually employed for determination of the biofilm mass could not be used throughout the experiments in this study since gave a false-positive result in control samples (i.e.…”

Involvement of quorum sensing genes in biofilm development and degradation of polycyclic aromatic hydrocarbons by a marine bacterium Pseudomonas aeruginosa N6P6

“…The las system consists of LasR (transcriptional regulatory protein) and LasI (autoinducer synthase). Whereas the rhl system consists of the RhlR and RhlI which encodes for transcriptional regulatory protein and autoinducer synthase, respectively (Cady et al 2012). The expression of lasI and rhlI was studied in P. aeruginosa N6P6 by semi-quantitative PCR.…”

Effect of Isoflavones Formononetin and Biochanin a to Tnhibit Biofilm Formation and Quorum sensing in Bacteria- Potential Application in the Prevention of Antibiotic Resistance in Bacteria

“…The biofilm inhibition assay was performed by microplate method as described by (Cady et al, 2012). Briefly, the plate culture of the micoorganisms (C.violaceum, P.aeruginosa, P.fluorescensand E.colias the case may be) was taken and a loopful of culture was inoculated into Luria Bertani broth.…”