In this situation only 1.5 times the amount of Ltnα is required, while 4.7 times Ltnβ is needed to achieve an MIC relative to their contribution when both lacticin CBL-0137 purchase 3147 peptides are present. Table 2 MIC data for lacticin 3147, and its individual peptides
Ltnα and Ltnβ, polymyxin B and polymyxin E alone and in combination E.coli 0157:H- MIC (μg/ml) Lacticin 3147 Polymyxin B Polymyxin E Lacticin 3147/ FIC Lacticin 3147/ FIC Polymyxin B Polymyxin E 231 (37.5 μM) 0.0586 0.0781 28.875/0.0073 0.250a 28.875/ 0.0049 0.188a (α :124.74, Β: 106.26) 28.875 / 0.0147* 0.376*a 14.4375 / 0.0195* 0.312*a Ltnα Polymyxin B Polymyxin E Ltnα/ FIC Ltnα/ FIC Polymyxin B Polymyxin E 187.11 (56.25 μM) 0.0586 0.0781 93.555 /
0.0073 0.625b 46.7775/ 0.0195 0.500a (1.5 X Ltnα) (6.0 X Ltnα in combin.) P5091 purchase (6.0 X Ltnα in combin.) Ltnβ Polymyxin B Polymyxin E Ltnβ/ FIC Ltnβ/ FIC Polymyxin B Polymyxin E 495.88 (175 μM) 0.0586 0.0781 61.9850 / 0.0147 0.376a 30.9925 / 0.0195 0.313a (4.7 X Ltnβ) (4.7 X Ltnβ in combin.) (4.7 X Ltnβ in combin.) FIC figures have been calculated as a result of triplicate experiments and indicate asynergy and bpartial synergy effects.*Alternative MIC and FIC data that allow for fixed levels of polymyxin across antimicrobial combinations, thus allowing for the calculation of the involvement of Ltnα and Ltnβ in synergy with polymyxin. Discussion We undertook a series of Amino acid investigations to determine whether lacticin 3147 acts synergistically with a range of clinically important antibiotics. Antibiotics encompassing many families and modes of action were chosen, including cephalosporins, polypeptides, glycopeptides, carbenems, and quinolones. Following this initial screen, it became clear that lacticin 3147 and the polymyxins acted synergistically. Polymyxins are a group of polypeptide antibiotics that exclusively target Gram
negative microorganisms. The five distinct members of this group, polymyxin A-E, were discovered in 1947 and are produced non-ribosomally by different Bacillus polymyxa species . Polymyxin B and polymyxin E (also referred to as colistin), have been used in clinical practice for decades in otic and ophthalmic solutions [12, 13]. Polymyxins are decapeptide antibiotics which consist of a heptapeptide ring, with polymyxin E differing from polymyxin B only by the presence of D-Leu in lieu of a D-Phe. This ring is linked to a tripeptide side-chain which carries an aliphatic chain attached via an amide bond to the amino terminus . The polymyxins carry five positive charges due to the presence of L-α-γ-diaminobutyric acids  and it has been SAR302503 established that the amphiphilic nature of this molecule gives it the ability to interact, bind and traverse the Gram negative outer membrane. The target molecule is lipopolysaccharide (LPS) , and specifically the lipid A component [16, 17].