Structure based virtual screening for identification of potential quorum sensing inhibitors against LasR master regulator in Pseudomonas aeruginosa.

Inter and intracellular communication in bacteria, which is known as quorum sensing (QS), is mediated by small diffusible signaling molecules known as autoinducers. QS regulates various virulence factors responsible for pathogenesis. Increasing resistance of microorganisms against traditional antibiotics has turned the focus towards the QS as it exerts less selective pressure preventing development of resistance among microorganisms. LasR, a transcription factor that controls QS in Pseudomonas aeruginosa, is an attractive therapeutic target for inhibitors. This study aimed to screen natural compounds as potential inhibitors of LasR. About 2603 compounds from ZINC database were virtually screened against the structure of LasR. Then after qualifying compounds were filtered on the parameters of Lipinski's rule and ADME. Six novel potential QS inhibiting compounds were selected on the basis of binding energy. Structures of LasR-ligand complexes were analysed to have insight of binding between inhibitors and target. It is pertinent to mention here that all the molecules are structurally different from 3-oxo-C12HSL,a native autoinducer of LasR, that play key role in formation of LasR dimer which is an active form of the protein to facilitate QS.

Effect of Cinnamon Oil on Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa.

Quorum sensing (QS) is a system of stimuli and responses in bacterial cells governed by their population density, through which they regulate genes that control virulence factors and biofilm formation. Despite considerable research on QS and the discovery of new antibiotics, QS-controlled biofilm formation by microorganisms in clinical settings has remained a problem because of nascent drug resistance, which requires screening of diverse compounds for anti-QS activities. Cinnamon is a dietary phytochemical that is traditionally used to remedy digestive problems and assorted contagions, which suggests that cinnamon might contain chemicals that can hinder the QS process. To test this hypothesis, the anti-QS activity of cinnamon oil against P. aeruginosa was tested, measured by the inhibition of biofilm formation and other QS-associated phenomena, including virulence factors such as pyocyanin, rhamnolipid, protease, alginate production, and swarming activity. To this end, multiple microscopy analyses, including light, scanning electron and confocal microscopy, revealed the ability of cinnamon oil to inhibit P. aeruginosa PAO1 biofilms and their accompanying extracellular polymeric substances. This work is the first to demonstrate that cinnamon oil can influence various QS-based phenomena in P. aeruginosa PAO1, including biofilm formation.

Molecular characterization and in vitro antifungal susceptibility of 80 clinical isolates of mucormycetes in Delhi, India.

Mucormycosis is a highly aggressive disease which is usually fatal in immunocompromised patients. The species of mucormycetes show significant differences in susceptibility to amphotericin B, azoles and terbinafine. The precise species level identification for this fungal group could be achieved by internal transcribed-spacer (ITS) region sequencing. Herein, we present the largest series of antifungal susceptibility data of molecularly characterised isolates of mucormycetes reported so far from India. Eighty isolates originating from 71 patients comprised 50 (62.5%) from pulmonary cases, 15 (19%) from rhino-orbital-cerebral, 13 (16.2%) from cutaneous and 2 (2.5%) from disseminated mucormycosis. ITS and D1/D2 regions sequencing of the isolates identified, Rhizopus arrhizus var. delemar (n = 25), R. arrhizus var. arrhizus (n = 15), R. microsporus (n = 17), R. stolonifer (n = 3), Syncephalastrum racemosum (n = 11), Apophysomyces elegans (n = 2), A. variabilis (n = 2), Lichtheimia ramosa (n = 3) and Mucor circinelloides f. lusitanicus (n = 2). Amplified fragment length polymorphism analysis was done to genotype Rhizopus isolates and revealed 5 clusters of R. arrhizus, which were well separated from R. microsporus. Amphotericin B was the most potent antifungal followed by posaconazole, itraconazole and isavuconazole. Etest and CLSI MICs of amphotericin B showed 87% agreement. Overall, the commonest underlying condition was uncontrolled diabetes mellitus. Records of 54 patients revealed fatalities in 28 cases.