Title:Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima:
Their Origins, Mechanisms of Action and Potential Applications
Volume: 22
Issue: 11
Author(s): David A. Phoenix, Frederick Harris and Sarah R. Dennison*
Affiliation:
- School of Pharmacy and Biological
Sciences, University of Central Lancashire, Preston PR1 2HE, UK
Keywords:
Antimicrobial peptides, pH-dependent, alkaline optimum, antibacterial, antiviral, antifungal, membranolysis, pore formation.
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.
