Furthermore, it is notable that recent research on CF patients from Ontario suggests that 25% of Ontario patients who are infected with P. aeruginosa are infected with one of two predominant
epidemic strains. It may be that the predominance of these epidemic strains is due to the GSK2118436 concentration production of specific antagonistic agents such as pyocins . This is an intriguing hypothesis MK-0518 that awaits further testing. As a start, we have confirmed that three of our clinical isolates produce toxic substances that kill or inhibit other clinical isolates (data not shown). Thus the antagonistic interactions we have studied here do happen among clinical isolates and are not just the consequence of using strains PA01 and PA14 as producers in our study . Understanding the way toxins such as pyocins kill P. aeruginosa strains, and how this is modulated by genetic relatedness, may also provide insight into the development of novel therapeutic interventions, for example by evolving pyocins specifically against strains that predominate in infections. They can thus be considered designer drugs [7, 23, 44, 45] and
will be a much more direct agent to treatment of the disease than the current practice of using broad spectrum antibiotics against which wide spread resistance exists . JPH203 Interestingly, pyocins are not new in a clinical setting: it has been shown that pyocins slow down the development of several forms of cancer in mammalian cells . Also, membrane vesicles produced by P. aeruginosa have been suggested as novel therapeutic agents . However they may be even more effective when used in a targeted way against known infections. The similarity between strains can then be used as a predictor of the intensity of the antagonistic
interaction and thus the effectiveness of the pyocin. Conclusions Using clinical and laboratory strains of Pseudomonas aeruginosa, Rebamipide we found that the level of antagonism between toxin producing and target strains is maximal at intermediate genetic and metabolic similarity between producer and target strain. We explained this result in the context of resource competition: resource competition is expected to be maximal for strains that are not your kin but also not completely unrelated since those strains do not share the same need for resources and are less likely to be a competitor. Our results suggest that the importance of antagonism and perhaps other social interactions between bacteria are modulated by the strength of resource competition. Methods Bacterial strains and culture conditions We used standard laboratory strains Pseudomonas aeruginosa strains PA01 and PA14 and 55 natural P. aeruginosa isolates collected from cystic fibrosis patients. Infection with P. aeruginosa is associated with increased morbidity and mortality for CF patients, irrespective of lung function.