Peptides Selected for Binding to a Virulent Strain of
            <i>Haemophilus influenzae</i>
            by Phage Display Are Bactericidal

Bishop-Hurley, Sharon L.; Schmidt, Francis J.; Erwin, Alice L.; Smith, Arnold L.

doi:10.1128/aac.49.7.2972-2978.2005

Cited by 28 publications

(21 citation statements)

References 40 publications

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“…c The intracellular glycogen concentration in the absence (triangular) and presence of 50 μM peptide AP1 (square) One of the selected phages carrying peptide AP1 can block the sugar phosphorylation process and retard cell growth. The IC 50 value of peptide AP1 was estimated to be 50 μM, comparable to other similar efforts (Bishop-Hurley et al 2005). However, as shown in Fig.…”

Section: Discussionmentioning

confidence: 96%

A dodecapeptide (YQVTQSKVMSHR) exhibits antibacterial effect and induces cell aggregation in Escherichia coli

Lin

Chen

Chang

et al. 2012

Appl Microbiol Biotechnol

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Antimicrobial peptides play an important role in the innate immune response and host defense mechanism. In the present study, we employed phage display technique to screen for inhibitors which may block the phosphoenolpyruvatedependent phosphotransferase system (PTS) pathway and hence retard cell growth. The recombinant histidine-containing phosphocarrier HPr protein was prepared as the target to screen for the tight binders from the phage-displayed random peptide library Ph.D.-12. The biopanning processes were performed and the binding capabilities of the selected phage were further estimated by enzyme-linked immunosorbent assay (ELISA). The single-stranded DNAs of the 20 selected phages were isolated, sequenced, and five corresponding peptides were synthesized. Only one of the five peptides, AP1 (YQVTQSK VMSHR) was found to inhibit the growth of Escherichia coli cells efficiently (IC₅₀~50 μM). Molecular modeling reveals that AP1 may block the EI-HPr interaction and phosphotransfer. Interestingly, AP1 was also found to induce cell aggregation in a concentration-dependent manner. Since glycogen accumulation has been attributed to biofilm formation, the effects of AP1 on the intracellular glycogen levels were measured. The results strongly indicate that the cell aggregation may be caused by the binding of peptide AP1 with HPr to block the interaction of dephosphorylated HPr with glycogen phosphorylase (GP). Because glycogen phosphorylase activity can be activated by HPr-GP interaction, the binding of AP1 to HPr would cause a decreasing rate of glycogen breakdown in M9 medium and accumulation of glycogen, which may lead to eventual cell aggregation. To the best of our knowledge, this is the first study to demonstrate that an inhibitor bound to a dephosphorylated HPr can decouple its regulatory function and induce cell aggregation.

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Section: Discussionmentioning

confidence: 96%

A dodecapeptide (YQVTQSKVMSHR) exhibits antibacterial effect and induces cell aggregation in Escherichia coli

Lin

Chen

Chang

et al. 2012

Appl Microbiol Biotechnol

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“…Similarly, combinatorial peptides selected against the human bacterial pathogen, Haemophilus influenzae, were shown to be strainspecific in their effects on bacterial cell growth (8). Such specificity of action contrasts with the typically broad spectrum membrane disruption caused by antimicrobial peptides.…”

Section: Discussionmentioning

confidence: 99%

“…Peptides that we have selected as ligand mimics have come from combinatorial libraries and are typically species-or strain-specific (7,8). These defense peptides differ from numerous naturally occurring antimicrobial peptides that function via disruption of cell membranes and that affect a broad range of prokaryotic and some eukaryotic microorganisms (9,10).…”

mentioning

confidence: 99%

Combinatorially selected defense peptides protect plant roots from pathogen infection

Fang

Laskey²,

Huang³

et al. 2006

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

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Agricultural productivity and sustainability are continually challenged by emerging and indigenous pathogens. Currently, many pathogens can be combated only with biocides or environmentally dangerous fumigants. Here, we report a rapid and pathogenspecific strategy to reduce infection by organisms that target plant roots. Combinatorially selected defense peptides, previously shown to effect premature encystment of Phytophthora capsici zoospores, were fused to maize cytokinin oxidase͞dehydrogenase as a display scaffold. When expressed in tomato roots, the peptidescaffold constructs were secreted and accumulated to sufficient concentrations in the rhizosphere to induce zoospore encystment and thereby deter taxis to the root surface. Pathogen infection was significantly inhibited in roots expressing bioactive peptides fused to the maize cytokinin oxidase͞dehydrogenase scaffold. This peptide-delivery technology is broadly applicable for rapid development of plant defense attributes against plant pathogens.disease resistance ͉ Phytophthora

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“…Of the four, human neutrophil peptide-1 is the most potent antimicrobial, with activity comparable to that of HBD2, against several strains of NTHI [47]. In a rat model of OM caused by direct inoculation with NTHI, recruitment of neutrophils to the middle ear peaked on day 4, with macrophage recruitment peaking on day 7, and maximal lymphocyte recruitment on day 14 [48].…”

Section: Defensinsmentioning

confidence: 99%

Innate Immunity and the Role of Defensins in Otitis Media

Underwood

2011

Curr Allergy Asthma Rep

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Otitis media is the most common pediatric disease in developed countries and a significant cause of morbidity and hearing loss in developing countries. The innate immune system is essential to protecting the middle ear from infection. Defensins, broad-spectrum cationic antimicrobial peptides, have been implicated in prevention of and the early response to acute otitis media; however, the mechanisms by which defensins and other antimicrobial molecules mediate this protection have not been completely elucidated. In both animal otitis media models and human middle ear epithelial cell culture models, β-defensins are highly induced and effectively kill the common pathogens associated with otitis media. We review the importance of innate immunity in protecting the middle ear and recent advances in understanding the roles of defensins and other antimicrobial molecules in the prevention and treatment of otitis media. The extremely high prevalence of otitis media, in spite of sophisticated innate and adaptive immune systems, is a vexing problem for clinicians and scientists. We therefore also review mechanisms by which bacteria evade innate immune defenses.

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Peptides Selected for Binding to a Virulent Strain of Haemophilus influenzae by Phage Display Are Bactericidal

Cited by 28 publications

References 40 publications

A dodecapeptide (YQVTQSKVMSHR) exhibits antibacterial effect and induces cell aggregation in Escherichia coli

A dodecapeptide (YQVTQSKVMSHR) exhibits antibacterial effect and induces cell aggregation in Escherichia coli

Combinatorially selected defense peptides protect plant roots from pathogen infection

Innate Immunity and the Role of Defensins in Otitis Media

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