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In Vitro Activity of OPT-80 against Clostridium difficile. Grit Ackermann, 2004.Clostridium difficile remains the major cause of nosocomial diarrhea . Reports on impaired susceptibility of C . difficile to metronidazole and vancomycin and frequent relapses of patients after therapy necessitate the search for new substances . With this study, the activity of OPT-80, a new macrocycle, against 207 C . difficile strains and against other obligately anaerobic bacteria was tested . OPT-80 showed high in vitro activity against all C . difficile strains tested . Particle-Based Multidimensional Multispecies Biofilm Model. Cristian Picioreanu, 2004.In this paper we describe a spatially multidimensional (two-dimensional [2-D] and three-dimensional [3-D]) particle-based approach for modeling the dynamics of multispecies biofilms growing on multiple substrates . The model is based on diffusion-reaction mass balances for chemical species coupled with microbial growth and spreading of biomass represented by hard spherical particles . Effectively, this is a scaled-up version of a previously proposed individual-based biofilm model . Predictions of this new particle-based model were quantitatively compared with those obtained with an established one-dimensional (1-D) multispecies model for equivalent problems . A nitrifying biofilm containing aerobic ammonium and nitrite oxidizers, anaerobic ammonium oxidizers, and inert biomass was chosen as an example . The 2-D and 3-D models generally gave the same results . If only the average flux of nutrients needs to be known, 2-D and 1-D models are very similar . However, the behavior of intermediates, which are produced and consumed in different locations within the biofilm, is better described in 2-D and 3-D models because of the multidirectional concentration gradients . The predictions of 2-D or 3-D models are also different from those of 1-D models for slowly growing or minority species in the biofilm . This aspect is related to the mechanism of biomass spreading or advection implemented in the models and should receive more attention in future experimental studies . Negative Control of Quorum Sensing by RpoN (  54) in Pseudomonas aeruginosa PAO1.Karin Heurlier, 2003.In Pseudomonas aeruginosa PAO1, the expression of several virulence factors such as elastase, rhamnolipids, and hydrogen cyanide depends on quorum-sensing regulation, which involves the lasRI and rhlRI systems controlled by N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone, respectively, as signal molecules . In rpoN mutants lacking the transcription factor 54, the expression of the lasR and lasI genes was elevated at low cell densities, whereas expression of the rhlR and rhlI genes was markedly enhanced throughout growth by comparison with the wild type and the complemented mutant strains . As a consequence, the rpoN mutants had elevated levels of both signal molecules and overexpressed the biosynthetic genes for elastase, rhamnolipids, and hydrogen cyanide . The quorum-sensing regulatory protein QscR was not involved in the negative control exerted by RpoN . By contrast, in an rpoN mutant, the expression of the gacA global regulatory gene was significantly increased during the entire growth cycle, whereas another global regulatory gene, vfr, was downregulated at high cell densities . In conclusion, it appears that GacA levels play an important role, probably indirectly, in the RpoN-dependent modulation of the quorum-sensing machinery of P . aeruginosa .
DNA Microarray Analyses of the Long-Term Adaptive Response of Escherichia coli to Acetate and Propionate. T. Polen, 2003.In its natural environment, Escherichia coli is exposed to short-chain fatty acids, such as acetic acid or propionic acid, which can be utilized as carbon sources but which inhibit growth at higher concentrations . DNA microarray experiments revealed expression changes during exponential growth on complex medium due to the presence of sodium acetate or sodium propionate at a neutral external pH . The adaptive responses to acetate and propionate were similar and involved genes in three categories . First, the RNA levels for chemotaxis and flagellum genes increased . Accordingly, the expression of chromosomal fliC'-'lacZ and flhDC'-'lacZ fusions and swimming motility increased after adaptation to acetate or propionate . Second, the expression of many genes that are involved in the uptake and utilization of carbon sources decreased, indicating some kind of catabolite repression by acetate and propionate . Third, the expression of some genes of the general stress response increased, but the increases were more pronounced after short-term exposure for this response than for the adaptive response . Adaptation to propionate but not to acetate involved increased expression of threonine and isoleucine biosynthetic genes . The gene expression changes after adaptation to acetate or propionate were not caused solely by uncoupling or osmotic effects but represented specific characteristics of the long-term response of E . coli to either compound .
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