To the identification of oxadiazoles among others as new drug leads

Consequently, the overall turmoil of ferric iron-binding protein regulation within the DPCPX biofilm might also affect the overall virulence of the biofilm towards the host tissue. Apart from its involvement in ferric iron-binding related proteins, the present findings show that A. actinomycetemcomitans regulated the metabolic rate within the biofilm. The most common up-regulated molecular function in the 11-species biofilm, compared to its 10-species variant, was that of 5S RNA binding. This enriched protein function of structural ribosomal constituents and the fact that more proteins were identified from the small ribosome CCMQ subunit, could easily be interpreted as an increase of bacterial growth ; however, given the fact that although the biofilms are cultured under stable growth conditions they do not display differences in bacterial numbers irrespective of the presence of A. actinomycetemcomitans, increased bacterial growth within the 11-species biofilm is an unlikely explanation for this observation. The increase of the ribosome content is rather explained by increased protein transport, fatty acid biosynthetic process, and protein initator methoionine removal, as also observed in the up-regulated biological process category. Indeed, around 3% more GO terms responsible for cell division were identified, but this might be counterbalanced by deceased ribosome biogenesis and protein folding processes. An altered metabolic rate was observed in an earlier study in a 3-species biofilm model, a trend that was also shown in this experimental model. In the presence of A. actinomycetemcomitans in the biofilm, biological processes like tricarboxylic acid cycle, fructose 1,6-bisphophate metabolism, and carbohydrate metabolism were enriched. By the present approach, it is not quite feasible to attribute these proteomic changes to one or another individual species, so at this stage they would have to be considered as a universal biofilm shift. Of note, fructose 1,6-bisphophate metabolism and carbohydrate metabolism were 2 of the 5 biological processes shared between these two kinds of biofilm variants. These two GO entities, together with glycolytic process, galactose metabolism, and arginine biosynthetic process, were enriched in absence of A. actinomycetemcomitans, indicating a strong alternation in the metabolic pathways of the biofilm. This may not be surprising, as for example, A. actinomycetemcomitans may utilize lactate from streptococci as energy source. On the other hand, many glucose transports in A. actinomycetemcomitans can also be inhibited, as consequence of using lactate as carbon source. These inhibited processes include a phosphoenolpyruvate : carbohydrate phosphotransferase system, a bacterial unique system for concomitant transport and phosphorylation of carbohydrates in many species.

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