Mechanism of antimicrobial action of indolicidin

Subbalakshmi, Chilukuri; Sitaram, N.

doi:10.1111/j.1574-6968.1998.tb12896.x

Cited by 395 publications

(237 citation statements)

References 23 publications

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“…(2) Although the average rmsf of the peptide backbone was only slightly higher for W11A than for IND, the average rmsf of residues 8-13 is significantly higher while the average rmsf of residues 1-5 is slightly lower in W11A than in IND. These data indicate that loss of the boat-shaped structure of W11A in DPC is driven by a disordering of residues [8][9][10][11][12][13]. (3) The orientation of the tryptophan side chains had a greater average fluctuation in W11A than for indolicidin in DPC.…”

Section: Results From the W11a Mutant Simulationmentioning

confidence: 88%

Cation−π Interactions Stabilize the Structure of the Antimicrobial Peptide Indolicidin near Membranes: Molecular Dynamics Simulations

Khandelia

Kaznessis

2006

J. Phys. Chem. B

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We implemented molecular dynamics simulations of the 13-residue antimicrobial peptide indolicidin (ILPWKWPWWPWRR-NH 2 ) in dodecylphosphocholine (DPC) and sodium dodecyl sulfate (SDS) micelles. In DPC, a persistent cation-π interaction between TRP11 and ARG13 defined the structure of the peptide near the interface. A transient cation-π interaction was also observed between TRP4 and the choline group on DPC lipids. We also implemented simulation of a mutant of indolicidin in the DPC micelle where TRP11 was replaced by ALA11. As a result of the mutation, the boat-shaped conformation is lost and the structure becomes significantly less defined. On the basis of this evidence, we argue that cation-π interactions determine the experimentally measured, well-defined boat-shaped structure of indolicidin. In SDS, the lack of such interactions and the electrostatic binding of the terminal arginine residues to the sulfate groups leads to an extended peptide structure. To the best of our knowledge, this is the first time that a cation-π interaction between peptide side chains has been shown to stabilize the structure of a small antimicrobial peptide. The simulations are in excellent agreement with available experimental measurements: the backbone of the peptide is more ordered in DPC than in SDS; the tryptophan side chains pack against the backbone in DPC and point away from the backbone in SDS; the rms fluctuation of the peptide backbone and peptide side chains is greater in SDS than in DPC; and the peptide backbone order parameters are higher in DPC than in SDS.

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Section: Results From the W11a Mutant Simulationmentioning

confidence: 88%

Cation−π Interactions Stabilize the Structure of the Antimicrobial Peptide Indolicidin near Membranes: Molecular Dynamics Simulations

Khandelia

Kaznessis

2006

J. Phys. Chem. B

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“…However, no morphological changes to the septa were observed with TEM. The peptides PR-39 [29], PR-26 [29], indolicidin [31] and microcin [28] were previously found to cause filamentation which may be caused by the inhibition or alteration of membrane proteins required for septum formation [4]. Sochaki and colleagues previously found that fluorescently labeled LL-37 more readily entered E. coli cells at the septal regions of dividing cells [30].…”

Section: Discussionmentioning

confidence: 99%

Investigation into the mechanism of action of the antimicrobial peptides Os and Os-C derived from a tick defensin

et al. 2015

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Highlights• Os and Os-C caused altered intracellular morphology of E. coli and B. subtilis.• Membrane effects were observed with fluorescence and TEM studies.• Os and Os-C were able to enter bacterial cells.• The peptides may have intracellular targets such as DNA.• Differences observed between Os and Os-C indicate dissimilar modes of action. AbstractOs and Os-C are two novel antimicrobial peptides, derived from a tick defensin, which have been shown to have a larger range of antimicrobial activity than the parent peptide, OsDef2. The aim of this study was to determine whether the peptides Os and Os-C are mainly membrane acting, or if these peptides have possible additional intracellular targets in Escherichia coli and Bacillus subtilis. Transmission electron microscopy revealed that both peptides adversely affected intracellular structure of both bacteria causing different degrees of granulation of the intracellular contents. At the minimum bactericidal concentrations, permeabilization as determined with the SYTOX green assay seemed not to be the principle mode of killing when compared to melittin. However, fluorescent triple staining indicated that the peptides caused permeabilization of stationary phase bacteria and TEM indicated membrane effects. Studies using fluorescently labeled peptides revealed that the membrane penetrating activity of Os and Os-C was similar to buforin II. Os-C was found to associate with the septa of B. subtilis. Plasmid binding studies showed that Os and Os-C binds E. coli plasmid DNA at a similar charge ratio as melittin. These studies suggest membrane activity for Os and Os-C with possible intracellular targets such as DNA.The differences in permeabilization at lower concentrations and binding to DNA between Os and Os-C, suggest that the two peptides have dissimilar modes of action.

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“…Mechanisms by which proteolytic activity could cause this replication defect include damaging bacteria directly and activating cationic antimicrobial peptides (28). We tested the hypothesis that a cathelicidin mediates Salmonella filamentation within macrophages because a synthetic active peptide of indolicidin, a bovine cathelicidin, has been reported to induce bacterial filamentation in vitro (29). Mice produce a single cathelicidin, named CRAMP.…”

Section: Intracellular Protease Activity Mediates Impaired Salmonellamentioning

confidence: 99%

Interplay between antibacterial effectors: A macrophage antimicrobial peptide impairs intracellular Salmonella replication

Rosenberger

Gallo

Finlay

2004

Proc. Natl. Acad. Sci. U.S.A.

215

200

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Antimicrobial peptides have established an important role in the defense against extracellular infections, but the expression of cationic peptides within macrophages as an antibacterial effector mechanism against intracellular pathogens has not been demonstrated. Macrophage expression of the murine cathelicidin-related antimicrobial peptide (CRAMP) was increased after infection by the intracellular pathogen Salmonella typhimurium, and this increase required reactive oxygen intermediates. By using CRAMP-deficient mice or synthetic CRAMP peptide, we found that CRAMP impaired Salmonella cell division in vivo and in vitro, resulting in long filamentous bacteria. This impaired bacterial cell division also depended on intracellular elastase-like serine protease activity, which can proteolytically activate cathelicidins. Macrophage serine protease activity induced filamentation and enhanced the activity of CRAMP in vitro. A peptidesensitive Salmonella mutant showed enhanced survival within macrophages derived from CRAMP-deficient mice, indicating that Salmonella can sense and respond to cationic peptides in the intracellular environment. Although cationic peptides have been hypothesized to have activity against pathogens within macrophages, this work provides experimental evidence that the antimicrobial arsenal of macrophages includes cathelicidins. These results show that intracellular reactive oxygen intermediates and proteases regulate macrophage CRAMP expression and activity to impair the replication of an intracellular bacterial pathogen, and they highlight the cooperativity between macrophage antibacterial effectors.

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Mechanism of antimicrobial action of indolicidin

Cited by 395 publications

References 23 publications

Cation−π Interactions Stabilize the Structure of the Antimicrobial Peptide Indolicidin near Membranes: Molecular Dynamics Simulations

Cation−π Interactions Stabilize the Structure of the Antimicrobial Peptide Indolicidin near Membranes: Molecular Dynamics Simulations

Investigation into the mechanism of action of the antimicrobial peptides Os and Os-C derived from a tick defensin

Interplay between antibacterial effectors: A macrophage antimicrobial peptide impairs intracellular Salmonella replication

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