With the emergence of multidrug-resistant and extensively drug-resistant bacterial pathogens, phage therapy and other alternative or additional therapeutic modalities are receiving resurgent attention. One of the major obstacles in developing effective phage therapies is the evolution of phage resistance in the bacterial host. When Pseudomonas aeruginosa was infected with a phage that uses O-antigen as receptor, phage resistances typically achieved through changing or loss of O-antigen structure. In this study, we showed that dsRNA phage phiYY uses core lipopolysaccharide as receptor and therefore efficiently kills the O-antigen deletion mutants. Furthermore, by phage training, we obtained PaoP5-m1, a derivative of dsDNA phage PaoP5, which is able to infect mutants with truncated O-antigen. We then generated a cocktail by mixing phiYY and PaoP5-m1 with additional three wide host range P. aeruginosa phages. The phage cocktail was effective against a diverse selection of clinical isolates of P. aeruginosa, and in the short-term constrained the appearance of the phage-resistant mutants that had beleaguered the effectiveness of single phage. Resistance to the 5phage cocktail emerges after several days, and requires mutations in both wzy and migA Thus, this study provides an alternative strategy for designing phage cocktail and phage therapy.
Popular interest in online communities has grown rapidly in recent years as a result of the widespread diffusion of Web 2.0 applications. However, the full values and potential of online communities cannot be realised without users' ongoing participation. Thus, this study aims at developing and empirically testing a research model to examine users' continuance intention to participate in an online community based on an extended information systems (IS) continuance model. Specifically, entertainment value and affective commitment are included in the IS continuance model and empirically examined in the context of online communities. A total of 240 returns collected from an online survey, which was conducted among users of a website bulletin board-based community in China, were analysed using partial least squares. The results reveal that users' continuance intention to participate in an online community is determined by both satisfaction and affective commitment. Satisfaction and affective commitment are, in turn, influenced by positive disconfirmations of purposive and entertainment values. The findings of this study contribute not only to theory building in online community continuance but also inform online community moderators in their effort to develop strategies for retaining their users.
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