Interleukin-8-Derived Peptide Has Antibacterial Activity

Björstad, Åse; Fu, Huamei; Karlsson, Anna; Dahlgren, Cláes; Bylund, Johan

doi:10.1128/aac.49.9.3889-3895.2005

Cited by 48 publications

(42 citation statements)

References 36 publications

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“…However, CXCL8 was consistently able to inhibit the growth of P. aeruginosa at concentrations of $0.5 mM. It has been reported that proteolytic processing of chemokines by bacterial proteinases did not interfere with their antibacterial activity (35), and that peptides derived from CXCL8 acquired bacteria killing properties (24). Consequently, we tested whether the unexpected antimicrobial activity of CXCL8 could be due to the presence of truncated CXCL8 peptides that have acquired antimicrobial activity.…”

Section: Cxcl14 Displays Bactericidal Effects Against Respiratory Tramentioning

confidence: 97%

“…However, chemokines have common structural features with classical AMPs including disulfide bridges, cationic amino acids, and amphi-pathic stretches. An initial screening for antimicrobial activity of chemokines revealed that large patches of positive electrostatic charges on the surface is an important characteristic to distinguish antimicrobial from nonantimicrobial chemokines (9), whereas cationic amino acids, which are often clustered in the C-terminal a-helix, are thought to interact with the negatively charged bacterial membranes (7,8,24). However, as described for CXCL6 (25) and for thrombocidin-1, a variant of CXCL7 lacking C-terminal alanine and aspartate (26), there are exceptions where key structural features for antimicrobial activity of chemokines lie in the N-terminal part.…”

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confidence: 99%

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CXCL14 Displays Antimicrobial Activity against Respiratory Tract Bacteria and Contributes to Clearance of Streptococcus pneumoniae Pulmonary Infection

Dai

Basilico

Cremona

et al. 2015

The Journal of Immunology

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CXCL14 is a chemokine with an atypical, yet highly conserved, primary structure characterized by a short N terminus and high sequence identity between human and mouse. Although it induces chemotaxis of monocytic cells at high concentrations, its physiological role in leukocyte trafficking remains elusive. In contrast, several studies have demonstrated that CXCL14 is a broad-spectrum antimicrobial peptide that is expressed abundantly and constitutively in epithelial tissues. In this study, we further explored the antimicrobial properties of CXCL14 against respiratory pathogens in vitro and in vivo. We found that CXCL14 potently killed Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus pneumoniae in a dose-dependent manner in part through membrane depolarization and rupture. By performing structure-activity studies, we found that the activity against Gram-negative bacteria was largely associated with the N-terminal peptide CXCL141–13. Interestingly, the central part of the molecule representing the β-sheet also maintained ∼62% killing activity and was sufficient to induce chemotaxis of THP-1 cells. The C-terminal α-helix of CXCL14 had neither antimicrobial nor chemotactic effect. To investigate a physiological function for CXCL14 in innate immunity in vivo, we infected CXCL14-deficient mice with lung pathogens and we found that CXCL14 contributed to enhanced clearance of Streptococcus pneumoniae, but not Pseudomonas aeruginosa. Our comprehensive studies reflect the complex bactericidal mechanisms of CXCL14, and we propose that different structural features are relevant for the killing of Gram-negative and Gram-positive bacteria. Taken together, our studies show that evolutionary-conserved features of CXCL14 are important for constitutive antimicrobial defenses against pneumonia.

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Section: Cxcl14 Displays Bactericidal Effects Against Respiratory Tramentioning

confidence: 97%

mentioning

confidence: 99%

CXCL14 Displays Antimicrobial Activity against Respiratory Tract Bacteria and Contributes to Clearance of Streptococcus pneumoniae Pulmonary Infection

Dai

Basilico

Cremona

et al. 2015

The Journal of Immunology

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“…However, considerable sequence similarity was detected between the C-terminal domain of IL-8/CXCL8 and Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), a cationic amphipathic antimicrobial peptide produced by Helicobacter pylori. 158 A corresponding synthetic peptide (amino acid residues 80 to 99 of IL-8/CXCL8) appears to possess significant antimicrobial activity regardless of some conflicting reports possibly reflecting different assay conditions. 156 The same peptide could be generated in vitro by acid hydrolysis of IL-8/ CXCL8, and it was suggested that colonization of the stomach by H. pylori may induce the local production of IL-8/CXCL8 that is further hydrolysed to the antimicrobial peptide.…”

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confidence: 99%

Antimicrobial peptides: The ancient arm of the human immune system

Wiesner¹,

Vilcinskas²

2010

Virulence

611

559

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The production of peptides and small proteins with microbicidal activity collectively called antimicrobial peptides (AMPs) is commonly considered to be a primitive mechanism of immunity and has been extensively studied in insects and other non-vertebrate organisms. In addition, a variety of AMPs present in amphibian skin secretion has been well characterised. There is now increasing evidence that AMPs play a crucial role in human immunity as well. Virtually all human tissues and cells typically exposed to microbes are able to produce AMPs. Important AMPs belonging to two structurally distinct classes, known as the defensins and the cathelicidins, are mainly produced by epithelial cells and neutrophils. AMPs significantly contributing to the chemical skin barrier are represented by dermcidin, psoriasin and RNase 7. The antimicrobial activity of saliva largely depends on histidine-rich AMPs known as histatins. Many more, in part less well-known AMPs and AMP-like proteins exist that exhibit various additional functions, apart from their antimicrobial properties. Among them, the neutrophil granule proteins azurocidin and cathepsin G are members of a family of serine-protease homologues called serprocidins and play a role in the regulation of the immune response and degradation of extracellular matrix proteins respectively. As another AMP-like protein of the neutrophil granule content, bactericidal/permeability increasing protein (BPI) is both able to permeabilise bacterial membranes and to function as an opsonin. The whey acidic protein (WAP) domain containing class of AMPs, including secretory leukocyte protease inhibitor (SLPI), elafin and trappin-2, is equally important in inhibition of neutrophil serine proteases and killing of microbes. Certain CC or CXC chemokines are known to possess antimicrobial properties and therefore are called kinocidins. Several kinocidins, including thrombocidin-1 and -2, are contained in the ?-granules of platelets. A cytoplasmic AMP described as ubiquicidin turned out to be identical with the strongly basic ribosomal protein S30. Proteolytic cleavage of the histone protein H2A in the stomach gives rise to an AMP initially described as buforin I. Adrenomedullin is a hormone-like AMP exhibiting vasodilatory and hypotensive effects. Lysozyme is mainly known for its cell wall degrading activity, but is also capable of non-enzymatic killing of bacteria. An iron-binding protein present in milk and other secretions named lactoferrin was shown to possess antimicrobial and antiviral activity and has been implicated in protection against cancer. Clinical studies on the treatment of infectious diseases have been performed with artificial peptides derived from human lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains and bovine indolicidin. Omiganan, representing an indolicidin derivative, has been demonstrated to be effective in the treatment of acne and catheter-related local infections and is currently considered to be the most promising AMP-based drug candidate

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“…Similar ␣-helical regions with flexible cationic tails have been identified as AMPs in other proteins, e.g., lactoferrampin (21). Moreover, this region of the IL-8 chemokine is reported to be antimicrobial (6). The structure of the C-terminal MIP-3␣ peptide bound to bacterial membrane mimetic SDS micelles shows an amphipathic helix highly similar to what is seen in the intact protein (Fig.…”

mentioning

confidence: 69%

“…It was shown recently that a 12-residue peptide from the C terminus of MIP-3␣ possesses antimicrobial activity (23). In addition, another chemokine, interleukin-8 (IL-8/CXCL8), is not antimicrobial itself, but a peptide corresponding to its C-terminal ␣-helical region is in fact bactericidal (6). This raises the question of whether the bulk of the anti-infective properties of MIP-3␣ can be linked to its highly cationic C-terminal ␣ helix.…”

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confidence: 99%

Human Macrophage Inflammatory Protein 3α: Protein and Peptide Nuclear Magnetic Resonance Solution Structures, Dimerization, Dynamics, and Anti-Infective Properties

Chan

Hunter

Tack

et al. 2008

Antimicrob Agents Chemother

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Human macrophage inflammatory protein 3␣ (MIP-3␣), also known as CCL20, is a 70-amino-acid chemokine which exclusively binds to chemokine receptor 6. In addition, the protein also has direct antimicrobial, antifungal, and antiviral activities. The solution structure of MIP-3␣ was solved by the use of two-dimensional homonuclear proton nuclear magnetic resonance (NMR). The structure reveals the characteristic chemokine fold, with three antiparallel ␤ strands followed by a C-terminal ␣ helix. In contrast to the crystal structures of MIP-3␣, the solution structure was found to be monomeric. Another difference between the NMR and crystal structures lies in the angle of the ␣ helix with respect to the ␤ strands, which measure 69 and ϳ56.5°in the two structures, respectively. NMR diffusion and pH titration studies revealed a distinct tendency for MIP-3␣ to form dimers at neutral pH and monomers at lower pH, dependent on the protonation state of His40. Molecular dynamics simulations of both the monomeric and the dimeric forms of MIP-3␣ supported the notion that the chemokine undergoes a change in helix angle upon dimerization and also highlighted the important hydrophobic and hydrogen bonding contacts made by His40 in the dimer interface. Moreover, a constrained N terminus and a smaller binding groove were observed in dimeric MIP-3␣ simulations, which could explain why monomeric MIP-3␣ may be more adept at receptor binding and activation. The solution structure of a synthetic peptide consisting of the last 20 residues of MIP-3␣ displayed a highly amphipathic ␣ helix, reminiscent of various antimicrobial peptides. Antimicrobial assays with this peptide revealed strong and moderate bactericidal activities against Escherichia coli and Staphylococcus aureus, respectively. This confirms that the C-terminal ␣-helical region of MIP-3␣ plays a significant part in its broad anti-infective activity.

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Interleukin-8-Derived Peptide Has Antibacterial Activity

Cited by 48 publications

References 36 publications

CXCL14 Displays Antimicrobial Activity against Respiratory Tract Bacteria and Contributes to Clearance of Streptococcus pneumoniae Pulmonary Infection

CXCL14 Displays Antimicrobial Activity against Respiratory Tract Bacteria and Contributes to Clearance of Streptococcus pneumoniae Pulmonary Infection

Antimicrobial peptides: The ancient arm of the human immune system

Human Macrophage Inflammatory Protein 3α: Protein and Peptide Nuclear Magnetic Resonance Solution Structures, Dimerization, Dynamics, and Anti-Infective Properties

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