- Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues
-
Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.
- An, Shi-qi,Murtagh, Julie,Twomey, Kate B.,Gupta, Manoj K.,O’Sullivan, Timothy P.,Ingram, Rebecca,Valvano, Miguel A.,Tang, Ji-liang
-
-
- INHIBITORS OF YEAST FILAMENTOUS GROWTH AND METHOD OF THEIR MANUFACTURE
-
The invention broadly relates to the use of α, β-unsaturated fatty acids to inhibit the filamentous growth of fungi and yeasts and to a method for producing same. In particular the invention relates to the use of optionally substituted C8 to C15 α, β-unsaturated fatty acids or salts, esters or amides thereof for inhibiting or retarding the yeast-to-mycelium transition of organisms having a dimorphic life cycle.
- -
-
Page/Page column 12-14
(2008/06/13)
-
- Radical Nature of Pathways to Alkene and Ester from Thermal Decomposition of Primary Alkyl Diacyl Peroxide
-
Thermal decomposition of a primary alkyl diacyl peroxide 2 is investigated.Dependence of product yields on temperature, viscosity, and solvent polarity is examined in a variety of media.The excess of the alkene disproportionation product 4 and the presence of ester 3 and acid 5 is argued to demonstrate the existence of a discrete acyloxy-alkyl geminate radical pair.Stereoselective deuterium labeling of 2 and subsequent 1H-NMR analysis of the resulting isotopomers of 4 confirm the radical nature of detected decomposition products.
- Ryzhkov, Lev R.
-
p. 2801 - 2808
(2007/10/03)
-