The capsular polysaccharide and type 1 fimbriae are two of the major surface-located virulence properties associated with the pathogenesis of Klebsiella pneumoniae. The capsule is an elaborate polysaccharide matrix that encases the entire cell surface and provides resistance against many host defense mechanisms. In contrast, type 1 fimbriae are thin adhesive thread-like surface organelles that can extend beyond the capsular matrix and mediate D-mannose-sensitive adhesion to host epithelial cells. These fimbriae are archetypical and consist of a major building block protein (FimA) that comprises the bulk of the organelle and a tip-located adhesin (FimH). It is assumed that the extended major-subunit protein structure permits the FimH adhesin to function independently of the presence of a capsule. In this study, we have employed a defined set of K. pneumoniae capsulated and noncapsulated strains to show that the function of type 1 fimbriae is actually impeded by the concomitant expression of a polysaccharide capsule. Capsule expression had significant effects on two parameters commonly used to define FimH function, namely, yeast cell agglutination and biofilm formation. Our data suggest that this effect is not due to transcriptional/translational changes in fimbrial gene/protein expression but rather the result of direct physical interference. This was further demonstrated by the fact that we could restore fimbrial function by inhibiting capsule synthesis. It remains to be determined whether the expression of these very different surface components occurs simply via random events of phase variation or in a coordinated manner in response to specific environmental cues.

Licochalcone A, an oxygenated chalcone isolated from the roots of Chinese licorice plant, inhibited the growth of both Leishmania major and Leishmania donovani promastigotes and amastigotes. The structure of the licochalcone A was established by mass and nuclear magnetic resonance spectroscopies and by synthesis, and its purity was verified by high-pressure liquid chromatography. The lished data from our group). The spread of drug resistance combined with other shortcomings of the available antileishmanial drugs emphasizes the importance of the development of new, effective, and safe drugs against leishmaniases.The discovery of new drugs from traditional medicine is not a new phenomenon. Worldwide, more than 100 clinically useful prescription drugs are derived from higher plants. About 74% of these came to the attention of pharmaceutical companies because of their use in traditional medicine (34). There are reports on the potential of plants as sources of new antiprotozoal agents (28,29). Licorice has been used in China for the treatment of gastric and duodenal ulcers, bronchial asthma, Addison's disease, food and drug poisoning, and skin diseases such as eczema and urticaria (35).The present study was designed to examine the potential antileishmanial activity of extracts of Chinese licorice roots. We found that an alcohol extract from the licorice roots inhibited the growth of L. major and L. donovani promastigotes. Following this finding, the compound with antileishmanial activity was purified from the plant by a bioassay-guided chemical fractionation of the extract. In this report, we show that licochalcone A, an oxygenated chalcone purified from the roots of Chinese licorice plant, exhibits potent antileishmanial activity. MATERUILS AND METHODSPlant extract. The extraction procedure was a modification of the method described by Ngam et al. (22). Briefly, 20 g of dried roots of licorice obtained from the Xinjiang Province of China were cut into small pieces, soaked in 350 ml of distilled water at room temperature overnight, and then 2550 on May 10, 2018 by guest http://aac.asm.org/ Downloaded from

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Our previous studies have shown that licochalcone A, an oxygenated chalcone, has antileishmanial and antimalarial activities, and alters the ultrastructure and function of the mitochondria of Leishmania spp. parasites. The present study was designed to investigate the antileishmanial activity and the mechanism of action of a group of new oxygenated chalcones. The tested oxygenated chalcones inhibited the in-vitro growth of Leishmania major promastigotes and Leishmania donovani amastigotes. Treatment of hamsters infected with L. donovani with intraperitoneal administration of two oxygenated chalcones resulted in a significant reduction of parasite load in the liver and the spleen compared with untreated control animals. The oxygenated chalcones also inhibited the respiration of the parasite and the activity of mitochondrial dehydrogenases. Electron microscopic studies illustrated that they altered the ultrastructure of the mitochondria of L. major promastigote. The data clearly indicate that this group of oxygenated chalcones has a strong antileishmanial activity and might be developed into a new antileishmanial drug. The antileishmanial activity of oxygenated chalcones might be the result of interference with function of the parasite mitochondria.