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

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

Zespół Smitha, Lemlego i Opitza--opis przypadku, wczesna diagnostyka.

Smith-Lemli-Opitz syndrome (SLOS) is one of the most frequent metabolic disorders in Poland and manifests itself with multiple congenital anomalies, psychomotor delay and intellectual disability. It is caused by mutations in DHCR7 gene, which codes one of the cholesterol biosynthesis enzymes. Clinical diagnosis of the syndrome is difficult due to lack of pathognomonic features and their variable expression. Despite high carrier frequency in Poland, SLO syndrome is rarely suspected and recognized. Its early diagnosis is essential, mainly because of high genetic risk (25%) as well as possibilities of treatment. Authors present a female-newborn, diagnosed with SLOS during the neonatal period. The diagnosis was based on biochemical and molecular tests. Mutations in DHCR7 gene have been found in both, the child and the parents