These results suggest that the bacteria posed little damage to the epithelial cells

CRT0066101 research buy which infact may be beneficial for their long term survival within the host tissue. The effect of phage on the adherence and invasion pattern of MRSA 43300 was determined using the in vitro model of cultured murine nasal epithelial cells. Phage at both the MOI (1, 10) was able to show highly significant reduction in all the three parameters as compared to untreated control. A pronounced decrease in the number of adhered bacterial population with negligible invasion and cytotoxicity was observed. Similarly phage was also able to significantly affect all the three parameters in clinical MRSA strains tested for these properties following interaction with phage. These results are in line with the findings of Clem [49] who showed that bacteriophages had protective effect on HEp-G2 cells from cellular damage and apoptosis induced by MRSA

isolates. A combination therapy with antimicrobials differing in their mechanisms Z-DEVD-FMK of action has been suggested to treat infections. This approach not only provides a broad spectrum of action due to synergistic effect but it also helps in preventing the emergence of drug-resistant subpopulation. It has been proposed that bacteria acquiring simultaneous resistance to both the phage and antibiotic is remote [13,14,50]. The results of this study suggest that when used in combination with phage, the frequency of emergence of spontaneous mutants towards mupirocin was effectively decreased to negligible levels (<10−9). To the best of our knowledge, the efficacy of lytic phage in decolonising the nares in an animal model has not been evaluated, though, the efficacy of phage born lytic enzymes has been assessed [51-53]. Hence, for assessing the therapeutic potential of phage MR-10 and mupirocin in eliminating

the nasal carriage of MRSA 43300, acute nasal colonization model (10 day) was experimentally established in healthy male BALB/c mice. MRSA colonisation was accomplished by putting a stress on the resident flora by increasing the inoculum load (106 CFU/ml, given twice) which helped in the dominance of MRSA 43300 in the nasal tissue over the resident flora. The treatment was started after Temsirolimus order allowing the P-type ATPase bacteria to colonise the nasal tissue of mice (in a period of 48 hours) in order to mimic the scenario prevalent in hospital and community settings, where the treatment is initiated in an already colonised person. Mice receiving two doses of phage MR-10 showed significant reduction (2.8 log cycles) on day 2 itself. Similarly, mupirocin given at a dose of 5 mg/kg (group 3) also showed significant reduction of 2 log cycles on day 2 and minimal bacterial load of 2.2 log CFU/gram on day 7. Both the agents given alone were able to significantly decrease the nasal load of MRSA 43300 by day 7.