RESUMEN
In cell-free Pseudomonas aeruginosa culture supernatants, we identified two compounds capable of activating an N-acylhomoserine lactone (AHL) biosensor. Mass spectrometry and NMR spectroscopy revealed that these compounds were not AHLs but the diketopiperazines (DKPs), cyclo(DeltaAla-L-Val) and cyclo(L-Pro-L-Tyr) respectively. These compounds were also found in cell-free supernatants from Proteus mirabilis, Citrobacter freundii and Enterobacter agglomerans [cyclo(DeltaAla-L-Val) only]. Although both DKPs were absent from Pseudomonas fluorescens and Pseudomonas alcaligenes, we isolated, from both pseudomonads, a third DKP, which was chemically characterized as cyclo(L-Phe-L-Pro). Dose-response curves using a LuxR-based AHL biosensor indicated that cyclo(DeltaAla-L-Val), cyclo(L-Pro-L-Tyr) and cyclo(L-Phe-L-Pro) activate the biosensor in a concentration-dependent manner, albeit at much higher concentrations than the natural activator N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL). Competition studies showed that cyclo(DeltaAla-L-Val), cyclo(L-Pro-L-Tyr) and cyclo(L-Phe-L-Pro) antagonize the 3-oxo-C6-HSL-mediated induction of bioluminescence, suggesting that these DKPs may compete for the same LuxR-binding site. Similarly, DKPs were found to be capable of activating or antagonizing other LuxR-based quorum-sensing systems, such as the N-butanoylhomoserine lactone-dependent swarming motility of Serratia liquefaciens. Although the physiological role of these DKPs has yet to be established, their activity suggests the existence of cross talk among bacterial signalling systems.
Asunto(s)
Dipéptidos/aislamiento & purificación , Bacterias Gramnegativas/metabolismo , Péptidos Cíclicos/aislamiento & purificación , Pseudomonas aeruginosa/metabolismo , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Técnicas Biosensibles , Comunicación Celular , Dipéptidos/química , Escherichia coli/metabolismo , Mediciones Luminiscentes , Estructura Molecular , Péptidos Cíclicos/química , FenotipoRESUMEN
The authors report their experience with 17 cases of cystic hygroma diagnosed in utero over a period of 6 years and followed to early infancy. Attempts were made to determine which ultrasonographic features were significant in predicting the outcome of this condition. The intrauterine course of the 6 fetuses with a normal karyotype and the 11 fetuses with Turner's syndrome or another form of aneuploidy was analysed to determine whether the size of the hygroma or the presence of septation or nonimmune hydrops could be used to predict the eventual outcome of the pregnancy. An association between the presence of septation and outcome was not demonstrated, but there was a strong association between septation and aneuploidy. Septate lesions were present in 6 of the 10 fetuses with Turner's syndrome and only 2 of the 6 fetuses with a normal karyotype. In this series the most significant features indicating a favourable outcome were the size of the hygroma (no fetus in which the hygroma had a diameter greater than 6 cm survived) and the change in size from the time of diagnosis until 24 weeks' gestation. Of the three fetuses in which the hygroma did not regress by 24 weeks, two died in utero.