Antimicrobial properties of arginine- and lysine-rich histones and involvement of bacterial outer membrane protease T in their differential mode of actions

Tagai, Chihiro; Morita, Shuu; Shiraishi, Taizo; Miyaji, Kazuyuki; Iwamuro, Shawichi

doi:10.1016/j.peptides.2011.09.005

Cited by 66 publications

(51 citation statements)

References 30 publications

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“…The mechanisms of action appear to divide into membrane permeabilizing effects or DNA‐binding and disruption of transcription, which is why some HDAPs are also under investigation for the treatment of cancer. Full length core histones (H2A, H2B, H3 and H4) have shown antimicrobial activity in vitro78 in animal79 and human80 physiology and have the ability to neutralize bacterial endotoxin.…”

Section: Molecular Basis Of Histone‐related Cellular and Tissue Injurymentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

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Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.

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Section: Molecular Basis Of Histone‐related Cellular and Tissue Injurymentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

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“…All four histone core subunits as well as H1 are capable of crossing cell membranes as well as sometimes mediating the crossing of other small molecules [9, 10]. Recent work has further investigated the antibacterial mechanism of histones H3 and H4 [11]. Additionally, several naturally occurring AMPs share sequence identity with portions of various histone subunits, implying that both whole and fragmented histone proteins may possess antibacterial properties [7, 8].…”

Section: 0 Introductionmentioning

confidence: 99%

Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms

Pavia

Spinella

Elmore

2012

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The increase in multidrug resistant bacteria has sparked an interest in the development of novel antibiotics. Antimicrobial peptides (AMPs) that operate by crossing the cell membrane may also have the potential to deliver drugs to intracellular targets. Buforin 2 (BF2) is an AMP that shares sequence identity with a fragment of histone subunit H2A and whose bactericidal mechanism depends on membrane translocation and DNA binding. Previously, novel histone-derived antimicrobial peptides (HDAPs) were designed based on properties of BF2, and DesHDAP1 and DesHDAP3 showed significant antibacterial activity. In this study, their DNA binding, permeabilization, and translocation abilities were assessed independently and compared to antibacterial activity to determine whether they share a mechanism with BF2. To investigate the importance of proline in determining the peptides' mechanisms of action, proline to alanine mutants of the novel peptides were generated. DesHDAP1, which shows significant similarities to BF2 in terms of secondary structure, translocates effectively across lipid vesicle and bacterial membranes, while the DesHDAP1 proline mutant shows reduced translocation abilities and antimicrobial potency. In contrast, both DesHDAP3 and its proline mutant translocate poorly, though the DesHDAP3 proline mutant is more potent. Our findings suggest that a proline hinge can promote membrane translocation in some peptides, but that the extent of its effect on permeabilization depends on the peptide's amphipathic properties. Our results also highlight the different antimicrobial mechanisms exhibited by histone-derived peptides and suggest that histones may serve as a source of novel AMPs with varied properties.

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“…However, the exact mechanism of action of AMPs remains unknown and controversial till now. It is generally accepted that AMPs kill bacterial cells by mainly targeting bacterial membranes and inhibiting bacterial reproduction by binding microbial intracellular organelles [38,39]. Additionally, the activity of AMPs and cell selectively has been attributed to several structural determinants within the primary sequence of the peptide such as charge, helicity, hydrophobicity and hydrophobic moment [40].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1

et al. 2014

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There is great interest in the development of antimicrobial peptides as a potentially novel class of antimicrobial agents. Several structural determinants are responsible for the antimicrobial and cytolytic activity of antimicrobial peptides. In our study, a new synthetic peptide analog, AamAP1-Lysine from the naturally occurring scorpion venom antimicrobial peptide AamAP1, was designed by modifying the parent peptide in order to increase the positive charge and optimize other physico-chemical parameters involved in antimicrobial activity. AamAP1-Lysine displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was in the range of 5 to 15 µM with a 10 fold increase in potency over the parent peptide. The hemolytic and antiproliferative activity of AamAP1-Lysine against eukaryotic mammalian cells was minimal at the concentration range needed to inhibit bacterial growth. The antibacterial mechanism analysis indicated that AamAP1-Lysine is probably inducing bacterial cell death through membrane damage and permeabilization determined by the release of β-galactosidase enzyme from peptide treated E. coli cells. DNA binding studies revealed that AamAP1-Lysine caused complete retardation of DNA migration and could display intracellular activities in addition to the membrane permeabilization mode of action reported earlier. In conclusion, AamAP1-Lysine could prove to be a potential candidate for antimicrobial drug development in future studies.

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Antimicrobial properties of arginine- and lysine-rich histones and involvement of bacterial outer membrane protease T in their differential mode of actions

Cited by 66 publications

References 30 publications

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms

Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1

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