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The Human Milk Protein-Lipid Complex HAMLET Sensitizes Bacterial Pathogens to Traditional Antimicrobial Agents

Figure 4

HAMLET-antibiotic combination treatment eradicates pneumococci during nasopharyngeal colonization.

(A and B) Mice were colonized with S. pneumoniae EF3030 for 48 hours, treated intranasally with various doses of gentamicin in the presence (red circles) or absence (black squares) of HAMLET (50 µg) for 6 hours, and the bacterial burden associated with the nasal lavage (A) and the nasopharyngeal tissue (B) was determined. Bacteria in nasal lavage and associated with the nasopharyngeal tissue were significantly more sensitive to gentamicin/HAMLET combination therapy than gentamicin alone. (C and D) Mice were colonized with the penicillin-resistant strain S. pneumoniae SP670 (MIC = 4 µg/mL) for 48 hours, treated intranasally with various doses of penicillin G in the presence (red circles) or absence (black squares) of HAMLET (50 µg) for 12 hours and the bacterial burden associated with the nasal lavage (C) and the nasopharyngeal tissue (D) was determined. Penicillin G alone had no effect on the bacterial burden in either the nasal lavage or in the tissue. However, combination therapy with HAMLET and penicillin caused a dose-dependent decrease in bacterial burden leading to eradication of colonization. The graph shows colonization data for individual mice, with the mean recovered bacteria and the standard deviation depicted. The results are based on experiments using groups of 6–10 mice. Statistics was performed using the unpaired Student t-test. Significance was indicated as follows: * = P<0.05, ** = P<0.01, ns = non-significant.

Figure 4

doi: https://doi.org/10.1371/journal.pone.0043514.g004