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BackgroundTranscriptome analysis was applied to characterize the physiological activities of Pseudomonas aeruginosa grown for three days in drip-flow biofilm reactors. Conventional applications of transcriptional profiling often compare two paired data sets that differ in a single experimentally controlled variable. In contrast this study obtained the transcriptome of a single biofilm state, ranked transcript signals to make the priorities of the population manifest, and compared ranki ngs for a priori identified physiological marker genes between the biofilm and published data sets.ResultsBiofilms tolerated exposure to antibiotics, harbored steep oxygen concentration gradients, and exhibited stratified and heterogeneous spatial patterns of protein synthetic activity. Transcriptional profiling was performed and the signal intensity of each transcript was ranked to gain insight into the physiological state of the biofilm population. Similar rankings were obtained from data sets published in the GEO database http://www.ncbi.nlm.nih.gov/geo. By comparing the rank of genes selected as markers for particular physiological activities between the biofilm and comparator data sets, it was possible to infer qualitative features of the physiological state of the biofilm bacteria. These biofilms appeared, from their transcriptome, to be glucose nourished, iron replete, oxygen limited, and growing slowly or exhibiting stationary phase character. Genes associated with elaboration of type IV pili were strongly expressed in the biofilm. The biofilm population did not indicate oxidative stress, homoserine lactone mediated quorum sensing, or activation of efflux pumps. Using correlations with transcript ranks, the average specific growth rate of biofilm cells was estimated to be 0.08 h-1.ConclusionsCollectively these data underscore the oxygen-limited, slow-growing nature of the biofilm population and are consistent with antimicrobial tolerance due to low metabolic activity.

Arginine enhanced the killing of Pseudomonas aeruginosa by ciprofloxacin and tobramycin under anaerobic, but not aerobic, growth conditions. Arginine or nitrate also enhanced the killing by these antibiotics in mature biofilms, reducing viable cell counts by a factor of 10 to 100 beyond that achieved by antibiotics alone.

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The first study of this series demonstrated that when shock is given for correct responses learning is accelerated as if it were given for wrong responses. It was concluded that the function of shock after the point of choice is "to make the animal respond more readily to the significant cues in the learning situation." (l,p.276) In this first experiment a rat of the shock-wrong group received about one-fifth of the amount of shock received by a rat in the shock-right group. And yet, the acceleration produced by shock for wrong responses was slightly in excess of that produced by shock for right responses. At that time we commented that "only further analysis can reveal whether or not this difference has any meaning." (1, p. 273) In view of these relations Professor H. A. Carr, in a personal communication to the senior author, 1 suggested that there might be two alternative explanations for shock-right effect. To quote Professor Carr:(a) "Shock exerts its effect upon the total reaction of the animal and the kind and degree of effect does not vary with the location at which the shock is given." This was essentially the position taken by us, except that we should add the restriction that such a statement referred only to shock after the point of 1 We are greatly indebted to Professor H. A. Carr for his critical comments on the experiments in this series and especially for his suggestions which led to the present experiment.