Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications

Journal article


Phoenix, D.A., Harris, F. and Dennison, S. (2021). Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications. Current Protein & Peptide Science. 22 (11), pp. 775-799. https://doi.org/10.2174/1389203722666210728105451
AuthorsPhoenix, D.A., Harris, F. and Dennison, S.
Abstract: A number of disorders and diseases are associated with conditions of high pH, and many conventional antibiotics lose their efficacy under these pH conditions, generating a need for novel antimicrobials. A potential solution to fulfill this need is Antimicrobial Peptides (AMPs) with high pH optima. This review shows that a variety of anionic and cationic AMPs with this pH dependency are produced by creatures across the eukaryotic kingdom, including rabbits, cattle, sheep, fish, crabs and frog. These AMPs exhibit activity against viruses, bacteria, and fungi that involve membrane interactions and appear to be facilitated by a variety of mechanisms that generally promote passage across membranes to attack intracellular targets, such as DNA or protein synthesisand/or membrane lysis. Some of these mechanisms are unknown, but those elucidated include the use of bacterial pores and transporters, the self-promoted uptake pathway, and established models of membrane interaction, such as the carpet mechanism, toroidal pore formation, the adoption of tilted peptide, and the SHM model. A variety of potential roles have been proposed for these AMPs, including use as antivirals, antibacterials, antifungals, adjuvants to antimicrobial therapy, biomarkers of disease, and probes for pathogenic microbes. In this review, these properties are described and discussed, emphasizing the antimicrobial mechanisms used by these AMPs and the pH dependency of these mechanisms.
KeywordsCell Biology; Molecular Biology; Biochemistry; General Medicine
Year2021
JournalCurrent Protein & Peptide Science
Journal citation22 (11), pp. 775-799
PublisherBentham Science Publishers
ISSN1389-2037
Digital Object Identifier (DOI)https://doi.org/10.2174/1389203722666210728105451
Publication dates
Print28 Jul 2021
Online27 Jul 2021
Publication process dates
Accepted10 Apr 2021
Deposited15 Oct 2021
Accepted author manuscript
License
File Access Level
Open
Additional information

The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/10.2174/1389203722666210728105451

Permalink -

https://openresearch.lsbu.ac.uk/item/8x871

Download files


Accepted author manuscript
Phoenix_CPPS_20021.doc
License: CC BY 4.0
File access level: Open

  • 145
    total views
  • 70
    total downloads
  • 6
    views this month
  • 2
    downloads this month

Export as

Related outputs

Bacterial susceptibility and resistance to modelin-5.
Dennison, S., Morton, L. H., Badiani, K., Harris, F. and Phoenix, D. (2023). Bacterial susceptibility and resistance to modelin-5. Soft Matter. 19 (42), pp. 8247-8263. https://doi.org/10.1039/d3sm01007d
Temporin B Forms Hetero-Oligomers with Temporin L, Modifies Its Membrane Activity, and Increases the Cooperativity of Its Antibacterial Pharmacodynamic Profile
Ferguson, Philip M., Clarke, M., Manzo, Giorgia, Hind, Charlotte K., Clifford, Melanie, Sutton, J., Lorenz, C., Phoenix, David A. and Mason, A. (2022). Temporin B Forms Hetero-Oligomers with Temporin L, Modifies Its Membrane Activity, and Increases the Cooperativity of Its Antibacterial Pharmacodynamic Profile. Biochemistry. 61 (11), pp. 1029-1040. https://doi.org/10.1021/acs.biochem.1c00762
PEGylation enhances the antibacterial and therapeutic potential of amphibian host defence peptides.
Dennison, S., Reddy, S.M., Morton, L.H.G., Harris, F., Badiani, K. and Phoenix, D.A (2021). PEGylation enhances the antibacterial and therapeutic potential of amphibian host defence peptides. Biochimica et biophysica acta. Biomembranes. 1864 (1), p. 183806. https://doi.org/10.1016/j.bbamem.2021.183806
Impacts of Metabolism and Organic Acids on Cell Wall Composition and Pseudomonas aeruginosa Susceptibility to Membrane Active Antimicrobials
Manzo, G., Gianfanti, F., Hind, C.K., Allison, L., Clarke, M., Hohenbichler, J., Limantoro, I., Martin, B., Do Carmo Silva, P., Ferguson, P.M., Hodgson-Casson, A., Fleck, R.A., Sutton, J., Phoenix, D.A. and Mason, A. (2021). Impacts of Metabolism and Organic Acids on Cell Wall Composition and Pseudomonas aeruginosa Susceptibility to Membrane Active Antimicrobials. ACS Infectious Diseases. 7 (8), pp. 2310-2323. https://doi.org/10.1021/acsinfecdis.1c00002
Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum.
Malik, E., Phoenix, D., Snape, T.J, Harris, F., Singh, J., Morton, .L.H.G. and Dennison, S. (2021). Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum. Molecular and Cellular Biochemistry. https://doi.org/10.1007/s11010-021-04181-7
A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy.
Manzo, G., Hind, C.K, Ferguson, P.M, Amison, R.T, Hodgson-Casson, A., Ciazynska, K.A., Weller, B.J, Clarke, M., Lam, C., Man, R.C ., O'Shaughnessy, B.G., Clifford, M., Bui, T., Drake, Alex F, Atkinson, R., Lam, J., Pitchford, S.C, Page, C.P, Phoenix, D.A, Lorenz, C., Sutton, J. and Mason, A. (2020). A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy. Communications biology. 3 (1), p. 697. https://doi.org/10.1038/s42003-020-01420-3
Biophysical studies on the antimicrobial activity of linearized esculentin 2EM
Malik, E., Phoenix, D., Badiana, K., Snape, T.J., Harris, F., Singh, J. and Dennison, S. (2019). Biophysical studies on the antimicrobial activity of linearized esculentin 2EM. BBA: Biomembranes. 1862 (2), p. 183141. https://doi.org/10.1016/j.bbamem.2019.183141
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. https://doi.org/10.1038/s41598-019-47327-w
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. https://doi.org/10.1038/s41598-018-37630-3
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. 566, pp. 185-193. https://doi.org/10.1016/j.ijpharm.2019.04.078
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. https://doi.org/10.1039/C8SM02374C
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). https://doi.org/https://www.doi.org/10.1007/s11010-009-0172-8
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). https://doi.org/10.1186/1742-4682-1-5
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. https://doi.org/10.2174/1389203719666180226155035
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. 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. https://doi.org/10.1371/journal.pone.0134679
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. https://doi.org/10.1016/j.biochi.2017.02.013
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. https://doi.org/10.1007/s00249-015-1094-x
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. https://doi.org/10.1021/acs.biochem.6b00101
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. https://doi.org/10.2174/0929866523666160511151215
PH dependent antimicrobial peptides and proteins, their mechanisms of action and potential as therapeutic agents
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). https://doi.org/10.3390/ph9040067
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. 28 (1), pp. 74-85. https://doi.org/10.1080/08982104.2016.1259628
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. BBA - Biochimica et Biophysica Acta. 1848 (5), pp. 1111 - 1118. https://doi.org/10.1016/j.bbamem.2015.01.014