Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis

Saiman, Lisa; Tabibi, Setareh; Starner, Timothy D.; Gabriel, Pablo; Winokur, Patricia L.; Jia, Hong Peng; McCray, Paul B.; Tack, Brian F.

doi:10.1128/aac.45.10.2838-2844.2001

Cited by 124 publications

(104 citation statements)

References 39 publications

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“…Enhancement of camp expression would be of considerable utility, as CAMP restored antimicrobial activity against antibiotic-resistant pathogens in sputum of CF patients (23) and enhanced responses against antibiotic-resistant pathogens in models of CF (24). Moreover, CAMP is a potent antisepsis agent; it blocked macrophage induction and enhanced survival of mice treated with lethal doses of LPS (23,25). The robust induction of camp observed above suggests that 1,25(OH) 2 D 3 analogues may be protective against sepsis.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression

Wang¹,

Nestel²,

Bourdeau

et al. 2004

The Journal of Immunology

1,389

614

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The hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)2D3 signals through the vitamin D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. In this study, we show that 1,25(OH)2D3 is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin β2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)2D3-dependent gene expression. 1,25(OH)2D3 induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)2D3 along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)2D3 induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)2D3 thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.

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Section: Resultsmentioning

confidence: 99%

Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression

Wang¹,

Nestel²,

Bourdeau

et al. 2004

The Journal of Immunology

1,389

614

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“…SMAP29 has broad-spectrum antimicrobial activity against Gramnegative and Gram-positive bacteria and fungi [11,43,45,46], is active in both low and high ionic strength conditions [11], and induces significant morphological alterations in bacterial surfaces [46,48]. Its activity against multiple antibiotic-resistant pathogens from patients with cystic fibrosis is of particular interest [47].…”

Section: Cationic Antimicrobial Peptidesmentioning

confidence: 99%

“…Cathelicidin-derived peptides represent a novel class of antimicrobial agents and warrant further development as prophylactic or therapeutic agents for CF lung disease. SMAP29 induces extensive ultrastructural damage in bacterial cells [47,48]. SMAP29 induces bacterial membrane blebs within 1 min, kills P. aeruginosa within 1 h and causes a dose-dependent, reversible decrease in transepithelial resistance within 5 h [47].…”

Section: Cationic Antimicrobial Peptidesmentioning

confidence: 99%

“…SMAP29 induces extensive ultrastructural damage in bacterial cells [47,48]. SMAP29 induces bacterial membrane blebs within 1 min, kills P. aeruginosa within 1 h and causes a dose-dependent, reversible decrease in transepithelial resistance within 5 h [47]. In transmission electron microscopy, SMAP29 induces damage characterized by rough surfaces containing extracellular debris and outer membranous blebs, thickened cell walls and electron dense cytoplasmic material (Fig.…”

Section: Cationic Antimicrobial Peptidesmentioning

confidence: 99%

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Antimicrobial peptides in animals and their role in host defences

Brogden

Ackermann

McCray

et al. 2003

International Journal of Antimicrobial Agents

414

287

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Domesticated animals have a large variety of antimicrobial peptides that serve as natural innate barriers limiting microbial infection or, in some instances, act as an integral component in response to inflammation or microbial infection. These peptides differ in size, composition, mechanisms of activity and range of antimicrobial specificities. They are expressed in many tissues, polymorphonuclear leukocytes, macrophages and mucosal epithelial cells. There is a small group of anionic antimicrobial peptides found in ruminants and a much larger group of cationic antimicrobial peptides found in all domesticated animals. The cationic peptides include linear, helical peptides, linear peptides rich in proline and cysteine-stabilized peptides with a b-sheet and are commonly referred to as cathelicidins and defensins. These peptides are generally broad-spectrum for Gram-positive bacteria, Gram-negative bacteria and fungi (e.g. myeloid antimicrobial peptides, a-, bdefensins, and protegrins) or are specific to one of these groups (e.g. porcine cecropin P1, Bac5, Bac7, PR-39 and prophenin). RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. Abstract Domesticated animals have a large variety of antimicrobial peptides that serve as natural innate barriers limiting microbial infection or, in some instances, act as an integral component in response to inflammation or microbial infection. These peptides differ in size, composition, mechanisms of activity and range of antimicrobial specificities. They are expressed in many tissues, polymorphonuclear leukocytes, macrophages and mucosal epithelial cells. There is a small group of anionic antimicrobial peptides found in ruminants and a much larger group of cationic antimicrobial peptides found in all domesticated animals. The cationic peptides include linear, helical peptides, linear peptides rich in proline and cysteine-stabilized peptides with a b-sheet and are commonly referred to as cathelicidins and defensins. These peptides are generally broad-spectrum for Gram-positive bacteria, Gram-negative bacteria and fungi (e.g. myeloid antimicrobial peptides, a-, b-defensins, and protegrins) or are specific to one of these groups (e.g. porcine cecropin P1, Bac5, Bac7, PR-39 and prophenin). Published by Elsevier B.V.

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“…Some even have activity against certain species of antibiotic-resistant bacteria. 84 Zasloff concludes 'Acquisition of resistance by a sensitive microbial strain against antimicrobial peptides is surprisingly improbable'. 85 Because it can be differentially spliced, the cathelicidin protein itself can respond to a range of very different microbial challenges.…”

Section: Our Therapeutic Approachmentioning

confidence: 99%

Immunostimulation in the era of the metagenome

Proal

Albert

Blaney³

et al. 2011

Cell Mol Immunol

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Microbes are increasingly being implicated in autoimmune disease. This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated. The standard of care for autoimmune disease remains the use of medications that slow the immune response, while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response. Immunostimulation is complicated by a cascade of sequelae, including exacerbated inflammation, which occurs in response to microbial death. Over the past 8 years, we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease. This intervention, designed to stimulate the innate immune response, has required a reevaluation of disease progression and amelioration. Paramount is the inherent conflict between palliation and microbicidal efficacy. Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms. Further studies are needed, but they will require careful planning to manage this immunopathology.

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Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis

Cited by 124 publications

References 39 publications

Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression

Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression

Antimicrobial peptides in animals and their role in host defences

Immunostimulation in the era of the metagenome

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