Low pH enhances the action of maximin H5 against Staphylococcus aureus and helps mediate lysylated phosphatidylglycerol induced resistance
Dennison, S, Morton, L, Harris, F and Phoenix, DA (2016). Low pH enhances the action of maximin H5 against Staphylococcus aureus and helps mediate lysylated phosphatidylglycerol induced resistance. Biochemistry. 55 (27), pp. 3735-3751.
|Authors||Dennison, S, Morton, L, Harris, F and Phoenix, DA|
Maximin H5 (MH5) is an amphibian antimicrobial peptide specifically targeting Staphylococcus aureus. At pH 6, the peptide showed an increased ability to penetrate (∆П = 6.2 mN m-1) and lyse (lysis = 48 %) S. aureus membrane mimics, which incorporated physiological levels of lysylated phosphatidylglycerol (Lys-PG, 60 %) as compared to pH 7 (∆П = 5.6 mN m-1 and lysis = 40 % at pH 7) where levels of Lys-PG are lower (40 %). The peptide therefore appears to have optimal function at pH levels known to be optimal for the organism’s growth. MH5 killed S. aureus (minimum inhibitory concentration = 90 µM) via membranolytic mechanisms that involved the stabilization of α-helical structure (circa 45-50 %) and which showed similarities to the ‘Carpet’ mechanism based on its ability to increase the rigidity (Cs-1 = 109.94 mN m-1) and thermodynamic stability (∆Gmix = -3.0) of physiologically relevant S. aureus membrane mimics at pH 6. Based on theoretical analysis this mechanism may involve the use of a tilted peptide structure and efficacy was noted to vary inversely with the Lys-PG content of S. aureus membrane mimics for each pH studied (R2 circa 0.97), which led to the suggestion that under biologically relevant conditions, low pH helps mediate Lys-PG induced resistance in S. aureus to MH5 antibacterial action. The peptide showed a lack of haemolytic activity (< 2 % haemolysis) and merits further investigation as a potential template for development as an anti-staphylococcal agent in medically and biotechnically relevant areas.
|Journal citation||55 (27), pp. 3735-3751|
|Publisher||London South Bank University|
|Digital Object Identifier (DOI)||doi:10.1021/acs.biochem.6b00101|
|23 Jun 2016|
|Publication process dates|
|Deposited||11 Apr 2017|
|Accepted||23 Jun 2016|
|Accepted author manuscript|
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