PH dependent antimicrobial peptides and proteins, their mechanisms of action and potential as therapeutic agents

Journal article


Malik, E, Dennison, SR, Harris, F and Phoenix, DA (2016). PH dependent antimicrobial peptides and proteins, their mechanisms of action and potential as therapeutic agents. Pharmaceuticals. 9 (4).
AuthorsMalik, E, Dennison, SR, Harris, F and Phoenix, DA
Abstract

© 2016 by the authors; licensee MDPI, Basel, Switzerland. Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

Keywords1115 Pharmacology And Pharmaceutical Sciences
Year2016
JournalPharmaceuticals
Journal citation9 (4)
PublisherMDPI
ISSN1424-8247
Digital Object Identifier (DOI)doi:10.3390/ph9040067
Publication dates
Print01 Nov 2016
Publication process dates
Deposited29 Aug 2017
Accepted26 Oct 2016
Accepted author manuscript
License
CC BY 4.0
Permalink -

https://openresearch.lsbu.ac.uk/item/871vq

  • 1
    total views
  • 36
    total downloads
  • 1
    views this month
  • 3
    downloads this month

Related outputs

Liposome Mediated-CYP1A1 Gene Silencing Nanomedicine Prepared Using Lipid Film-Coated Proliposomes as a Potential Treatment Strategy of Lung Cancer
Zhang, M, Wang, Q, Wan, K, Ahmed, W, Phoenix, D, Zhang, Z, Elrayess, MA, Elhissi, A and Sun, X (2019). Liposome Mediated-CYP1A1 Gene Silencing Nanomedicine Prepared Using Lipid Film-Coated Proliposomes as a Potential Treatment Strategy of Lung Cancer. International Journal of Pharmaceutics.
Biophysical investigation into the antibacterial action of modelin-5-NH2
Dennison, S, Hauß, T, Badiani, K, Harris, F and Phoenix, D (2019). Biophysical investigation into the antibacterial action of modelin-5-NH2. Soft Matter.
Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity
Manzo, G, Ferguson, PM, Gustilo, VB, Hind, CK, Clifford, M, Bui, TT, Drake, AF, Atkinson, RA, Sutton, JM, Batoni, G, Lorenz, CD, Phoenix, DA and Mason, AJ (2019). Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity. Scientific Reports. 9 (1), p. 1385.
Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities
Manzo, G., Ferguson, P.M., Hind, C.K., Clifford, M., Gustilo, V.B., Ali, H., Bansal, S.S., Bui, T.T., Drake, A.F., Atkinson, R.A., Sutton, J.M., Lorenz, C.D., Phoenix, D. and Mason, A.J. (2019). Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities. Scientific Reports. 9.
The effect of C-terminal amidation on the efficacy and selectivity of antimicrobial and anticancer peptides
Harris, F, Dennison, S, Bhatt, T, Singh, J and Phoenix, DA (2009). The effect of C-terminal amidation on the efficacy and selectivity of antimicrobial and anticancer peptides. Molecular and Cellular Biochemistry. 332 (43).
Anionic host defence peptides from the plant kingdom: their anticancer activity and mechanisms of action
Harris, F, Prabhu, S, R Dennison, S, J Snape, T, Lea, R, Mura, M and Phoenix, DA (2016). Anionic host defence peptides from the plant kingdom: their anticancer activity and mechanisms of action. Protein and peptide letters. 23 (8), pp. 676-687.
Investigation of hydrophobic moment and hydrophobicity properties for transmembrane α-helices
Wallace, J, Daman, OA, Harris, F and Phoenix, DA (2004). Investigation of hydrophobic moment and hydrophobicity properties for transmembrane α-helices. Theoretical Biology and Medical Modelling. 1 (5).
An Atlas of Anionic Antimicrobial Peptides from Amphibians
Dennison, SR, Harris, F, Mura, M and Phoenix, DA (2018). An Atlas of Anionic Antimicrobial Peptides from Amphibians. Current Protein & Peptide Science. 19 (8), pp. 823-838.
Bacterial resistance to host defence peptides
Phoenix, DA, Dennison, SR and Harris, F (2016). Bacterial resistance to host defence peptides. in: Host Defense Peptides and Their Potential as Therapeutic Agents Springer International Publishing. pp. 161-204
Prediction of Peptide and Protein Propensity for Amyloid Formation
Famlia, C, Dennison, SR, Quintas, A and Phoenix, DA (2015). Prediction of Peptide and Protein Propensity for Amyloid Formation. PLoS ONE. 10.
Ethanol-based proliposome delivery systems of paclitaxel for in vitro application against brain cancer cells
Najlah, M, Jain, M, Wan, KW, Ahmed, W, Albed Alhnan, M, Phoenix, DA, Taylor, KMG and Elhissi, A (2016). Ethanol-based proliposome delivery systems of paclitaxel for in vitro application against brain cancer cells. Journal of Liposome Research.
The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5.
Dennison, SR, Mura, M, Harris, F, Morton, LH, Zvelindovsky, A and Phoenix, DA (2015). The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5. Biochim Biophys Acta. 1848 (5), pp. 1111 - 1118.
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.
Investigations into the potential anticancer activity of Maximin H5
Dennison, SR, Harris, F and Phoenix, DA (2017). Investigations into the potential anticancer activity of Maximin H5. Biochimie. 137 (June), pp. 29-34.
The effect of amidation on the behaviour of antimicrobial peptides
Mura, M, Wang, J, Zhou, Y, Pinna, M, Zvelindovsky, A, Dennison, SR and Phoenix, DA (2016). The effect of amidation on the behaviour of antimicrobial peptides. European Biophysics Journal. 45 (3), pp. 195-207.