e. by day 5 itself. Also the decrease in bacterial load was significantly greater than the monotherapy groups (group 2 and 3) on all days. Also
selleck peak phage titres were observed on day 2 and declined thereafter. In the co-therapy group, phage titres persisted till day 3 only and no plaque was seen on day 5. As phages are highly specific and thus replicate and increase in number at the expense of their respective host bacteria [53,54] hence no phage activity observed on different days, points towards complete eradication of their host bacteria (MRSA 43300) following treatment with phage. Complete eradication of bacteria was possible due to the combined administration of two agents after allowing successful colonisation of the bacteria in the nasal tissue of mice. The presence of S. aureus in the nose elicits a subclinical immune response, as reported in an earlier study where sero-conversion occurred after carriage was established . Also the host elicits a number of immune factors that constantly impose pressure to eliminate the foreign colonising population [34,56]. Neutrophils are the most PCI-34051 in vivo prominent cellular component of the innate immune system and act as an essential primary defence against S. aureus . In this study, neutrophil recruitment
was studied in terms of MPO GSK2118436 in vitro levels in all the groups. MPO levels were highest in the untreated colonised group on all post treatment days. The groups receiving phage and mupirocin alone showed peak MPO levels on day 2 and the activity declined to the basal value by day 7. This observation correlates well with the declining bacterial load seen on day 7 in both these groups. Combination therapy group exhibited maximum reduction in MPO levels on day 2 onwards. These results further confirm the efficacy of phages in eliminating the colonized S. aureus from the anterior nares of mice. PRKD3 The results of histopathological examination of control (untreated) and treated nasal tissue also substantiated these observations. In the
combined therapy group, minimal or no tissue infiltration was seen and the skin of nasal mucosa appeared normal. The present study indicates that the phage when given along with mupirocin was able to effectively eradicate the colonising population due to their combined action. The dual approach showed maximum nasal protection (better than use of either agent alone i.e. monotherapy) in terms of reduced nasal bacterial load, reduced catalase and MPO levels; with complete elimination of MRSA 43300 occurring by day 5. Coates et al.  advocated the need to develop potent bactericidal agent than mupirocin on the ground that the newer agents might reduce the relapse rate, clearing the patient of S. aureus for a longer period of time than mupirocin. The success obtained with this dual approach is based on the fact that mupirocin being a bacteriostatic antibiotic was able to significantly halt the multiplication and growth of S.