coli strains again revealed synergism between lacticin 3147 and the polymyxins. An FIC index value of 0.248 was obtained when lacticin
3147 and polymyxin B were combined against 0157:H- while the corresponding lacticin 3147 and polymyxin E FIC value was 0.188. When lacticin 3147 and polymyxin B were combined against E. coli DH5α and EC101, FIC indices of 0.188 and 0.5 were obtained, respectively. In addition, an FIC index of 0.188 was determined when lacticin 3147 and polymyxin E were combined for these two target strains. A number of additional assays were carried out in order to determine if the benefits of combining lacticin 3147 and the see more polymyxins in broth extended to Gram positive targets. For this purpose Bacillus cereus 8079, Enterococcus faecium DO and Staphylococcus aureus 5247 were selected as representative LY3039478 indicator strains. It was established that, while some partial synergy between lacticin 3147 and polymyxin B was observed with respect to B. cereus 8079 and S. aureus 5247 (FIC = 0.62 and 0.75, respectively), the other combinations resulted in an additive or indifferent outcome. Given that the most notable outcome from the study was the synergistic activity of lacticin 3147 and the polymyxins against some Gram negative targets, further investigations were carried out to determine how the respective
components of lacticin 3147, i.e. Ltnα and Ltnβ, perform individually in the presence of polymyxin B/E. Selecting the sensitive strain E. coli 0157:H- as a target, we were able to evaluate the contribution Immune system of the individual α and β peptides to this phenomenon (Table 2). Taking into consideration the molecular weights and 1:1 ratio at which α and β are combined, we can derive the relative amount (μg/ml) of each individual NVP-AUY922 cost peptide present when lacticin 3147 (Ltnα and Ltnβ combined in a 1:1 ratio) is synergistic with polymyxin B/E. With this information we can compare the action of α and β alone to the same amount of each peptide present in whole lacticin 3147 in each case of synergy. Although various degrees of synergy exist due to the different combinations and concentrations assessed, only those that yielded the greatest synergy with respect to
lacticin 3147 are listed in Table 1. Obtaining such a high degree of synergy was not possible with the single peptides, Ltnα and Ltnβ. For this reason additional synergy values/FIC data for lacticin 3147 in combination with polymyxin B and E has been included in Table 2. This provides a means by which the contribution of the individual lacticin 3147 components can be derived by focusing on a fixed level of polymyxin B/E in each case of synergy. Hence, it is apparent that, when combined with a set concentration of polymyxin B and E, 6 times more Ltnα alone is required to achieve the level of synergy obtained when both Ltnα and Ltnβ are present. In contrast, only 4.7 times Ltnβ alone is required to achieve a corresponding level of activity in the absence of Ltnα.