Antimicrobial properties of a lipid interactive α-helical peptide VP1 against Staphylococcus aureus bacteria (original) (raw)
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Diversity of antimicrobial peptides and their mechanisms of action
Biochimica Et Biophysica Acta-reviews on Biomembranes, 1999
Antimicrobial peptides encompass a wide variety of structural motifs. Many peptides have α-helical structures. The majority of these peptides are cationic and amphipathic but there are also hydrophobic α-helical peptides which possess antimicrobial activity. In addition, some β-sheet peptides have antimicrobial activity and even antimicrobial α-helical peptides which have been modified to possess a β-structure retain part of their antimicrobial activity. There are also antimicrobial peptides which are rich in a certain specific amino acid such as Trp or His. In addition, antimicrobial peptides exist with thio-ether rings, which are lipopeptides or which have macrocyclic Cys knots. In spite of the structural diversity, a common feature of the cationic antimicrobial peptides is that they all have an amphipathic structure which allows them to bind to the membrane interface. Indeed, most antimicrobial peptides interact with membranes and may be cytotoxic as a result of disturbance of the bacterial inner or outer membranes. Alternatively, a necessary but not sufficient property of these peptides may be to be able to pass through the membrane to reach a target inside the cell. The interaction of these peptides with biological membranes is not just a function of the peptide but is also modulated by the lipid components of the membrane. It is not likely that this diverse group of peptides has a single mechanism of action, but interaction of the peptides with membranes is an important requirement for most, if not all, antimicrobial peptides.
Host-defense Antimicrobial Peptides: Importance of Structure for Activity
Current Pharmaceutical Design, 2002
Antimicrobial peptides are important components of innate immunity in species across the evolutionary scale. Unlike therapeutically used antibiotics, this class of peptides exert their activity by permeabilizing bacterial membranes. Despite the seemingly common mechanism of action, there is considerable variation in their primary structures, length and number of positive charges. Host-defense antimicrobial peptides have been the subject of extensive biophysical studies with a view at delineate structural requirements for activity. In this article, the structures of host defence antibacterial peptides and the structural requirements for activity are reviewed. LINEAR ANTIMICROBIAL PEPTIDES Linear antimicrobial peptides can be categorized mainly into two broad classes : (i) peptides which have a propensity to assume amphiphilic α-helical structure and (ii) peptides which are rich in certain amino acids and do not have propensity for α-helical structure. The sequences of linear antibacterial peptides whose structures are discussed are summarized in Table 1.
Journal of Biological Chemistry, 2005
In the present study, the 26-residue peptide sequence Ac-KWKSFLKTFKSAVKTVLHTALKAISSamide (V 681 ) was utilized as the framework to study the effects of peptide hydrophobicity/ hydrophilicity, amphipathicity, and helicity (induced by single amino acid substitutions in the center of the polar and nonpolar faces of the amphipathic helix) on biological activities. The peptide analogs were also studied by temperature profiling in reversed-phase high performance liquid chromatography, from 5 to 80 °C, to evaluate the self-associating ability of the molecules in solution, another important parameter in understanding peptide antimicrobial and hemolytic activities. A higher ability to self-associate in solution was correlated with weaker antimicrobial activity and stronger hemolytic activity of the peptides. Biological studies showed that strong hemolytic activity of the peptides generally correlated with high hydrophobicity, high amphipathicity, and high helicity. In most cases, the D-amino acid substituted peptides possessed an enhanced average antimicrobial activity compared with L-diastereomers. The therapeutic index of V 681 was improved 90-and 23fold against Gram-negative and Gram-positive bacteria, respectively. By simply replacing the central hydrophobic or hydrophilic amino acid residue on the nonpolar or the polar face of these amphipathic derivatives of V 681 with a series of selected D-/L-amino acids, we demonstrated that this method has excellent potential for the rational design of antimicrobial peptides with enhanced activities.
Structure-function studies of amphiphilic antibacterial peptides
Journal of Medicinal Chemistry, 1993
The synthesis of 11 peptides, ranging in composition from 9 to 17 amino acid residues, by solid-phase methodology was accomplished with the purpose of studying how the amphiphilic and hydrophobic character, the size of the molecule, and the charge distribution modulate the antibacterial activity. It was found that peptides composed of 16 and 17 amino acid residues, with high hydrophobic (mainly due to Trp or Phe) and hydrophilic (due to Lys) character distributed along opposite amphiphilic faces, showed considerable antibacterial activity against clinically isolated bacteria together with Gram positive and Gram negative ATCC bacterial strains. However, the hemolytic capacity of the peptides was also significant. Decreasing the hydrophobic character of the molecule by replacing Trp or Phe with Leu residues while maintaining the basic contribution of Lys drastically reduced the hemolytic activity and only slightly decreased the bioactivity. Peptides composed of 9-10 amino acid residues with high hydrophobic and basic nature possess antibacterial activity but, in general, are less active than the larger counterpart peptides. By replacing all Trp residues of a short peptide by Leu residues, the activity was considerably reduced. Circular dichroism studies and antibacterial assays showed that shorter peptides with very low helical content, and thus deprived of amphiphilic character, still have appreciable bioactivity. This observation, coupled with the fact that due to their small size they cannot span the bacterial outer lipid bilayer, may suggest different mechanisms of action for long-chain vis-a-vis short-chain peptides.
Effect of hydrophobic modifications in antimicrobial peptides
Advances in Colloid and Interface Science, 2014
With increasing resistance development against conventional antibiotics, there is an urgent need to identify novel approaches for infection treatment. Antimicrobial peptides may offer opportunities in this context, hence there has been considerable interest in identification and optimization of such peptides during the last decade in particular, with the long-term aim of developing these to potent and safe therapeutics. In the present overview, focus is placed on hydrophobic modifications of antimicrobial peptides, and how these may provide opportunities to combat also more demanding pathogens, including multi-resistant strains, yet not provoking unacceptable toxic responses. In doing so, physicochemical factors affecting peptide interactions with bacterial and eukaryotic cell membranes are discussed. Throughout, an attempt is made to illustrate how physicochemical studies on model lipid membranes can be correlated to results from bacterial and cell assays, and knowledge from this translated into therapeutic considerations.
Activity and characterization of a pH-sensitive antimicrobial peptide
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2019
Antimicrobial peptides (AMPs) have been an area of great interest, due to the high selectivity of these molecules toward bacterial targets over host cells and the limited development of bacterial resistance to these molecules throughout evolution. Previous work showed that when Histidine was incorporated into the peptide C18G it lost antimicrobial activity. The role of pH on activity and biophysical properties of the peptide was investigated to explain this phenomenon. Minimal Inhibitory Concentration (MIC) results demonstrated that decreased media pH increased antimicrobial activity. Tricholorethanol (TCE) quenching and red-edge excitation spectroscopy (REES) showed a clear pH dependence on peptide aggregation in solution. Trp fluorescence was used to monitor binding to lipid vesicles and demonstrated the peptide binds to anionic bilayers at all pH values tested, however, binding to zwitterionic bilayers was enhanced at pH 7 and 8 (above the His pKa). Dual Quencher Analysis (DQA) confirmed the peptide inserted more deeply in PC:PG and PE:PG membranes, but could insert into PC bilayers at pH conditions above the His pKa. Bacterial membrane permeabilization assays which showed enhanced membrane permeabilization at pH 5 and 6 but vesicle leakage assays indicate enhanced permeabilization of PC and PC:PG bilayers at neutral pH. The results indicate the ionization of the His side chain affects the aggregation state of the peptide in solution and the conformation the peptide adopts when bound to bilayers, but there are likely more subtle influences of lipid composition and properties that impact the ability of the peptide to form pores in membranes.
Interactions of an anionic antimicrobial peptide with Staphylococcus aureus membranes
Biochemical and Biophysical Research Communications, 2006
The antimicrobial activity of the anionic peptide, AP1 (GEQGALAQFGEWL), was investigated. AP1 was found to kill Staphylococcus aureus with an MLC of 3 mM and to induce maximal surface pressure changes of 3.8 mN m À1 over 1200 s in monolayers formed from lipid extract of S. aureus membranes. FTIR spectroscopy showed the peptide to be a-helical (100%) in the presence of vesicles formed from this lipid extract and to induce increases in their fluidity (Dm circa 0.5 cm À1 ). These combined data show that AP1 is able to function as an a-helical antimicrobial peptide against Gram-positive bacteria and suggest that the killing mechanism used by the peptide involves interactions with the membrane lipid headgroup region. Moreover, this killing mechanism differs strongly from that previously reported for AP1 against Gram-negative bacteria, indicating the importance of considering the effects of membrane lipid composition when investigating the structure/function relationships of antimicrobial peptides.