DOCSLIB.ORG

Antimicrobial Defense Cathelicidins for Enhanced Topical Postsecretory

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antimicrobial Defense Cathelicidins for Enhanced Topical Postsecretory Postsecretory Processing Generates Multiple Cathelicidins for Enhanced Topical Antimicrobial Defense This information is current as Masamoto Murakami, Belen Lopez-Garcia, Marissa Braff, of October 1, 2021. Robert A. Dorschner and Richard L. Gallo J Immunol 2004; 172:3070-3077; ; doi: 10.4049/jimmunol.172.5.3070 http://www.jimmunol.org/content/172/5/3070 Downloaded from References This article cites 35 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/172/5/3070.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 1, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Postsecretory Processing Generates Multiple Cathelicidins for Enhanced Topical Antimicrobial Defense1 Masamoto Murakami, Belen Lopez-Garcia, Marissa Braff, Robert A. Dorschner, and Richard L. Gallo2 The production of antimicrobial peptides and proteins is essential for defense against infection. Many of the known human antimicrobial peptides are multifunctional, with stimulatory activities such as chemotaxis while simultaneously acting as natural antibiotics. In humans, eccrine appendages express DCD and CAMP, genes encoding proteins processed into the antimicrobial peptides dermcidin and LL-37. In this study we show that after secretion onto the skin surface, the CAMP gene product is processed by a serine protease-dependent mechanism into multiple novel antimicrobial peptides distinct from the cathelicidin LL-37. These peptides show enhanced antimicrobial action, acquiring the ability to kill skin pathogens such as Staphylococcus aureus and Candida albicans. Furthermore, although LL-37 may influence the host inflammatory response by stimulating IL-8 Downloaded from release from keratinocytes, this activity is lost in subsequently processed peptides. Thus, a single gene product encoding an important defense molecule alters structure and function in the topical environment to shift the balance of activity toward direct inhibition of microbial colonization. The Journal of Immunology, 2004, 172: 3070–3077. eptides with antimicrobial activity are found throughout activity becomes available at the most external interface, providing nature and are known to be important for the immune de- an inhibitory barrier to infection. P fense of plants, insects, and animals (1). Many of these The clinical consequences of antimicrobial peptide expression http://www.jimmunol.org/ peptides exhibit a broad spectrum of antimicrobial activity, inhib- are demonstrated by observations that patients with atopic derma- iting or killing Gram-positive and Gram-negative bacteria, fungi, titis lack the ability to increase cathelicidins and defensins in re- and viruses. In mammals, antimicrobial peptides belonging to the sponse to inflammatory stimuli (15). As patients with atopic der- cathelicidin family have been shown to be important for the anti- matitis are uniquely susceptible to infection compared with normal microbial efficacy of neutrophils, macrophages, and mast cells (2– individuals or those with elevated expression, as seen in psoriasis, 6). In addition, epithelia of lung, gut, urinary bladder, oral mucosa, this first-line immune defense mechanism appears to have an es- and skin produce antimicrobial peptides of the defensin and cathe- sential function for resistance against skin infections. Similarly, licidin families constitutively or in response to injury (7–9). At the patients with Kostmann syndrome, a rare inherited disorder char- by guest on October 1, 2021 epithelial interface with the external environment, these molecules acterized by frequent infections and neutrophil dysfunction, have a are thought to serve as a rapid first line defense for inhibition of deficiency in production and processing of cathelicidin (16). Such microbial proliferation and invasion. emerging clinical associations support the need to further explore In mammalian skin, cathelicidins have been directly shown to be the function and regulation of this evolutionarily ancient aspect of essential for defense against invasive bacterial infection by group the human immune system. A streptococcus (10). Found in abundance in neutrophils and mast Most antimicrobial peptides are synthesized as inactive prepro- cells, the cathelicidins are expressed at relatively low levels in proteins that require enzymatic processing for release of active normal keratinocytes, but are rapidly induced during inflammation peptides. Lack of processing, such as seen in ␣-defensins from (11). The recruitment of cathelicidin-rich cells and the increase in Panath cells of matrilysin-deficient mice (17), leads to impaired expression by the epithelial keratinocytes lead to accumulation of clearance of infection in the gut. Similarly, inhibition of processing cathelicidins in wound fluid and in the overlying crust (12). Re- of porcine cathelicidins by elastase impairs bacterial clearance in cently, cathelicidins and dermcidin have also been found consti- wounds (18). The enzymatic processing of cathelicidins from a tutively produced by the eccrine apparatus and secreted constitu- pro-protein to a two-component solution consisting of the cathelin tively into human sweat (13, 14). In this scenario, antimicrobial prodomain and the C-terminal cationic antimicrobial peptide, LL- 37, can have multiple consequences for immune defense. The Division of Dermatology, University of California, and Veterans Affairs San Diego cathelin domain is itself antimicrobial and functions to inhibit cys- Healthcare Center, San Diego, CA 92161 teine proteases such as cathepsin L (19). LL-37, although func- Received for publication August 27, 2003. Accepted for publication December tional as a broad spectrum antimicrobial, can also stimulate che- 15, 2003. motaxis and angiogenesis by binding formyl peptide receptor- The costs of publication of this article were defrayed in part by the payment of page like-1 (20, 21) and improve re-epithelialization to enhance wound charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. repair (22). In this study we determined whether additional antimicrobial 1 This work was supported by a Veterans Affairs merit award and National Institutes of Health Grants RO1AR45676 and AI52453 (to R.L.G.), the Japan-North America peptides are present in the most superficial barrier topically pro- Medical Exchange Foundation (to M.M.), and the Ramon Areces Foundation (to vided by human sweat. Our findings suggest that human catheli- B.L.-G.). cidin is further processed and enables a shift in biological activity 2 Address correspondence and reprint requests to Dr. Richard L. Gallo, MC 911B, 3350 LaJolla Village Drive, San Diego, CA 92161. E-mail address: rgallo@vapop. toward antimicrobial function and away from the ability to stim- ucsd.edu ulate a host response. Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 The Journal of Immunology 3071 Materials and Methods Mass spectrometry and protein sequence analysis Sweat collection and processing Mass spectrometry was performed by Center for Mass Spectrometry, The Scripps Research Institute (La Jolla, CA). MALDI-MS spectra were ob- Sweat was collected on paper tissues (Kimwipes; Kimberly-Clark, Neenah, tained with a Voyager DE-RP MALDI-TOF mass spectrometer (PerSep- WI) from healthy volunteers after exercise as previously described (13). tive Biosystems, Framingham, MA) equipped with a nitrogen laser (337 After collection, 20 ml of sweat was centrifuged at 2000 ϫ g for 15 min nm, 3-ns pulse). Spectra were collected in the reflector mode. The accel- at 4°C, filtered through a 0.20-␮l filter (Acrodisc syringe filter, 0.2 ␮m, low erating voltage in the ion source was 20 kV. Data were acquired with a protein binding; Fisher Scientific, Tustin, CA), and frozen at Ϫ80°C. For transient recorder with 2-ns resolution. The matrix used in this work was some experiments sweat was lyophilized to dryness, then suspended in 400 a-cyano-4-hydroxycinnamic acid dissolved in water/acetonitrile (1/1, v/v) ␮l of distilled water (DW3; cell culture grade, endotoxin free; Life Tech- to give a saturated solution at room temperature. To prepare the sample for nologies, Grand Island, NY). For analysis of LL37 processing by sweat, 1.6 ␮ analysis, 1 ␮l of the peptide solution (containing 1–10 pmol of protein in nmol of LL-37 synthetic peptide was incubated in 50 l of sweat for 0, 1, ␮ 6,and24hat37or4°C. In some experiments proteinase inhibitors in- 0.1% trifluoroacetic acid) was added to 1 l of the matrix solution and cluding mixed protease inhibitor mixture (1 tablet/10 ml; Roche, Indianap- applied to a stainless steel sample plate. The mixture was then allowed
Load more

Recommended publications
  • Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections
    Review Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections 1,2, , 3, 4 3 Bapi Pahar * y , Stefania Madonna y , Arpita Das , Cristina Albanesi and Giampiero Girolomoni 5 1 Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA 2 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70118, USA 3 IDI-IRCCS, Dermopathic Institute of the Immaculate IDI, 00167 Rome, Italy; [email protected] (S.M.); [email protected] (C.A.) 4 Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA; [email protected] 5 Section of Dermatology, Department of Medicine, University of Verona, 37126 Verona, Italy; [email protected] * Correspondence: [email protected] Authors contributed equally. y Received: 4 August 2020; Accepted: 7 September 2020; Published: 10 September 2020 Abstract: Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing cytokine production and attracting and regulating the activity of immune cells. AMPs are scarcely expressed in normal skin, but their expression increases when skin is injured by external factors, such as trauma, inflammation, or infection. LL-37 complexed to self-DNA acts as autoantigen in psoriasis and lupus erythematosus (LE), where it also induces production of interferon by plasmocytoid dendritic cells and thus initiates a cascade of autocrine and paracrine processes, leading to a disease state.
    [Show full text]
  • The Avian Heterophil ⇑ Kenneth J
    Developmental and Comparative Immunology xxx (2013) xxx–xxx Contents lists available at SciVerse ScienceDirect Developmental and Comparative Immunology journal homepage: www.elsevier.com/locate/dci The avian heterophil ⇑ Kenneth J. Genovese ,1, Haiqi He 1, Christina L. Swaggerty 1, Michael H. Kogut U.S. Department of Agriculture, Agricultural Research Service, Food and Feed Safety Research Unit, College Station, TX 77845, USA article info abstract Article history: Heterophils play an indispensable role in the immune defense of the avian host. To accomplish this Available online xxxx defense, heterophils use sophisticated mechanisms to both detect and destroy pathogenic microbes. Detection of pathogens through the toll-like receptors (TLR), FC and complement receptors, and other Keywords: pathogen recognition receptors has been recently described for the avian heterophil. Upon detection of Heterophil pathogens, the avian heterophil, through a network of intracellular signaling pathways and the release Innate immunity and response to cytokines and chemokines, responds using a repertoire of microbial killing mechanisms Avian including production of an oxidative burst, cellular degranulation, and production of extracellular matri- Poultry ces of DNA and histones (HETs). In this review, the authors describe the recent advances in our under- Granulocyte standing of the avian heterophil, its functions, receptors and signaling, identified antimicrobial products, cytokine and chemokine production, and some of the effects of genetic selection on heterophils and their functional characteristics. Published by Elsevier Ltd. 1. Introduction including its functions, receptors, intracellular signaling, antimi- crobial products, and the known genetics related to its functional Avian species, specifically domestic poultry, are constantly ex- efficiency. posed to a myriad of pathogens and microbes in their environ- ments.
    [Show full text]
  • Antimicrobial Activity of Cathelicidin Peptides and Defensin Against Oral Yeast and Bacteria JH Wong, TB Ng *, RCF Cheung, X Dan, YS Chan, M Hui
    RESEARCH FUND FOR THE CONTROL OF INFECTIOUS DISEASES Antimicrobial activity of cathelicidin peptides and defensin against oral yeast and bacteria JH Wong, TB Ng *, RCF Cheung, X Dan, YS Chan, M Hui KEY MESSAGES Mycosphaerella arachidicola, Saccharomyces cerevisiae and C albicans with an IC value of 1. Human cathelicidin LL37 and its fragments 50 3.9, 4.0, and 8.4 μM, respectively. The peptide LL13-37 and LL17-32 were equipotent in increased fungal membrane permeability. inhibiting growth of Candida albicans. 6. LL37 did not show obvious antibacterial activity 2. LL13-37 permeabilised the membrane of yeast below a concentration of 64 μM and its fragments and hyphal forms of C albicans and adversely did not show antibacterial activity below a affected mitochondria. concentration of 128 μM. Pole bean defensin 3. Reactive oxygen species was detectable in the exerted antibacterial activity on some bacterial yeast form after LL13-37 treatment but not in species. untreated cells suggesting that the increased membrane permeability caused by LL13-37 might also lead to uptake of the peptide, which Hong Kong Med J 2016;22(Suppl 7):S37-40 might have some intracellular targets. RFCID project number: 09080432 4. LL37 and its fragments also showed antifungal 1 JH Wong, 1 TB Ng, 1 RCF Cheung, 1 X Dan, 1 YS Chan, 2 M Hui activity against C krusei, and C tropicalis. 5. A 5447-Da antifungal peptide with sequence The Chinese University of Hong Kong: 1 School of Biomedical Sciences homology to plant defensins was purified from 2 Department of Microbiology king pole beans by chromatography on Q- Sepharose and FPLC-gel filtration on Superdex * Principal applicant and corresponding author: 75.
    [Show full text]
  • Primitive Teleost Fish Cathelicidin Antimicrobial Peptides in a Biological Activities of the Multiple Distinctive Structural
    Distinctive Structural Hallmarks and Biological Activities of the Multiple Cathelicidin Antimicrobial Peptides in a Primitive Teleost Fish This information is current as of October 1, 2021. Xu-Jie Zhang, Xiang-Yang Zhang, Nu Zhang, Xia Guo, Kai-Song Peng, Han Wu, Long-Feng Lu, Nan Wu, Dan-Dan Chen, Shun Li, Pin Nie and Yong-An Zhang J Immunol published online 15 April 2015 http://www.jimmunol.org/content/early/2015/04/15/jimmun Downloaded from ol.1500182 Supplementary http://www.jimmunol.org/content/suppl/2015/04/15/jimmunol.150018 Material 2.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published April 15, 2015, doi:10.4049/jimmunol.1500182 The Journal of Immunology Distinctive Structural Hallmarks and Biological Activities of the Multiple Cathelicidin Antimicrobial Peptides in a Primitive Teleost Fish Xu-Jie Zhang,*,† Xiang-Yang Zhang,*,† Nu Zhang,*,† Xia Guo,*,† Kai-Song Peng,*,‡ Han Wu,* Long-Feng Lu,*,† Nan Wu,* Dan-Dan Chen,*,† Shun Li,* Pin Nie,* and Yong-An Zhang* Cathelicidin antimicrobial peptides (CAMPs) represent a crucial component of the innate immune system in vertebrates.
    [Show full text]
  • Effect of Dermcidin, an Antimicrobial Peptide, on Body Fat Mobilization in Normal Mice
    111 Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice Kyung-Ah Kim1,*, Sun-O Ka1,*, Woo Sung Moon2, Ho-Keun Yi3, Young-Hoon Lee4, Kang-Beom Kwon5, Jin-Woo Park1 and Byung-Hyun Park1 Departments of 1Biochemistry and 2Pathology, Medical School and Institute for Medical Sciences, 3Biochemistry and 4Oral Anatomy, Dental School and Institute of Oral Biosciences, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea 5Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea (Correspondence should be addressed to B-H Park; Email: [email protected]) *(K-A Kim and S-O Ka contributed equally to this work) Abstract Dermcidin (DCD), an antimicrobial peptide that is secreted tissues obtained from Ad-b-gal-injected mice. The gene by sweat glands, is reportedly a human homolog of mouse expression profiles revealed an upregulation of hormone- proteolysis-inducing factor. This study was conducted to sensitive lipase and adipose fatty acid-binding protein, both of investigate the effect of DCD on body fat mobilization. The which are involved in adipocyte lipolysis, in Ad-DCD- expression level of DCD in the livers of Ad-DCD-injected injected mice, and this lipolytic effect of DCD paralleled the mice was higher than in those of Ad-b-galactosidase (Ad-b- increase of circulating tumor necrosis factor-a (TNF-a)level gal)-injected mice 7 days after injection. In addition, injection that was observed. The perilipin levels in adipose tissue were with the Ad-DCD virus led to decreased body weight and decreased in Ad-DCD-injected mice when compared with epididymal fat mass when compared with controls.
    [Show full text]
  • Cathelicidin-Related Innate Immunity Role
    The Journal of Immunology Lysozyme-Modified Probiotic Components Protect Rats against Polymicrobial Sepsis: Role of Macrophages and Cathelicidin-Related Innate Immunity1 Heng-Fu Bu,*† Xiao Wang,*† Ya-Qin Zhu,*‡ Roxanne Y. Williams,* Wei Hsueh,† Xiaotian Zheng,† Ranna A. Rozenfeld,‡ Xiu-Li Zuo,† and Xiao-Di Tan2*†‡ Severe sepsis is associated with dysfunction of the macrophage/monocyte, an important cellular effector of the innate immune system. Previous investigations suggested that probiotic components effectively enhance effector cell functions of the immune system in vivo. In this study, we produced bacteria-free, lysozyme-modified probiotic components (LzMPC) by treating the probiotic bacteria, Lactobacillus sp., with lysozyme. We showed that oral delivery of LzMPC effectively protected rats against lethality from polymicrobial sepsis induced by cecal ligation and puncture. We found that orally administrated LzMPC was engulfed by cells such as macrophages in the liver after crossing the intestinal barrier. Moreover, LzMPC-induced protection was associated with an increase in bacterial clearance in the liver. In vitro, LzMPC up-regulated the expression of cathelicidin-related antimicrobial peptide (CRAMP) in macrophages and enhanced bactericidal activity of these cells. Furthermore, we demonstrated that surgical stress or cecal ligation and puncture caused a decrease in CRAMP expression in the liver, whereas enteral admin- istration of LzMPC restored CRAMP gene expression in these animals. Using a neutralizing Ab, we showed that protection against sepsis by LzMPC treatment required endogenous CRAMP. In addition, macrophages from LzMPC-treated rats had an enhanced capacity of cytokine production in response to LPS or LzMPC stimulation. Together, our data suggest that the protective effect of LzMPC in sepsis is related to an enhanced cathelicidin-related innate immunity in macrophages.
    [Show full text]
  • Human Cathelicidin LL-37 Is a Chemoattractant for Eosinophils and Neutrophils That Acts Via Formyl-Peptide Receptors
    Original Paper Int Arch Allergy Immunol 2006;140:103–112 Received: January 3, 2005 Accepted after revision: December 19, 2005 DOI: 10.1159/000092305 Published online: March 24, 2006 Human Cathelicidin LL-37 Is a Chemoattractant for Eosinophils and Neutrophils That Acts via Formyl-Peptide Receptors a a b G. Sandra Tjabringa Dennis K. Ninaber Jan Wouter Drijfhout a a Klaus F. Rabe Pieter S. Hiemstra a b Departments of Pulmonology, and Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden , The Netherlands Key Words ting using antibodies directed against phosphorylated Eosinophils Neutrophils Chemotaxis Antimicrobial ERK1/2. Results: Our results show that LL-37 chemoat- peptides Innate immunity Lung infl ammation tracts both eosinophils and neutrophils. The FPR antag- onistic peptide tBoc-MLP inhibited LL-37-induced che- motaxis. Whereas the FPR agonist fMLP activated ERK1/2 Abstract in neutrophils, LL-37 did not, indicating that fMLP and Background: Infl ammatory lung diseases such as asth- LL-37 deliver different signals through FPRs. Conclu- ma and chronic obstructive pulmonary disease (COPD) sions: LL-37 displays chemotactic activity for eosinophils are characterized by the presence of eosinophils and and neutrophils, and this activity is mediated via an FPR. neutrophils. However, the mechanisms that mediate the These results suggest that LL-37 may play a role in in- infl ux of these cells are incompletely understood. Neu- fl ammatory lung diseases such as asthma and COPD. trophil products, including neutrophil elastase and anti- Copyright © 2006 S. Karger AG, Basel microbial peptides such as neutrophil defensins and LL- 37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive im- Introduction munity.
    [Show full text]
  • Innate Immune System of Mallards (Anas Platyrhynchos)
    Anu Helin Linnaeus University Dissertations No 376/2020 Anu Helin Eco-immunological studies of innate immunity in Mallards immunity innate of studies Eco-immunological List of papers Eco-immunological studies of innate I. Chapman, J.R., Hellgren, O., Helin, A.S., Kraus, R.H.S., Cromie, R.L., immunity in Mallards (ANAS PLATYRHYNCHOS) Waldenström, J. (2016). The evolution of innate immune genes: purifying and balancing selection on β-defensins in waterfowl. Molecular Biology and Evolution. 33(12): 3075-3087. doi:10.1093/molbev/msw167 II. Helin, A.S., Chapman, J.R., Tolf, C., Andersson, H.S., Waldenström, J. From genes to function: variation in antimicrobial activity of avian β-defensin peptides from mallards. Manuscript III. Helin, A.S., Chapman, J.R., Tolf, C., Aarts, L., Bususu, I., Rosengren, K.J., Andersson, H.S., Waldenström, J. Relation between structure and function of three AvBD3b variants from mallard (Anas platyrhynchos). Manuscript I V. Chapman, J.R., Helin, A.S., Wille, M., Atterby, C., Järhult, J., Fridlund, J.S., Waldenström, J. (2016). A panel of Stably Expressed Reference genes for Real-Time qPCR Gene Expression Studies of Mallards (Anas platyrhynchos). PLoS One. 11(2): e0149454. doi:10.1371/journal. pone.0149454 V. Helin, A.S., Wille, M., Atterby, C., Järhult, J., Waldenström, J., Chapman, J.R. (2018). A rapid and transient innate immune response to avian influenza infection in mallards (Anas platyrhynchos). Molecular Immunology. 95: 64-72. doi:10.1016/j.molimm.2018.01.012 (A VI. Helin, A.S., Wille, M., Atterby, C., Järhult, J., Waldenström, J., Chapman, N A S J.R.
    [Show full text]
  • Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Yazan H
    University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 8-2013 Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Yazan H. Akkam University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/etd Part of the Biochemistry Commons, Medicinal and Pharmaceutical Chemistry Commons, and the Molecular Biology Commons Recommended Citation Akkam, Yazan H., "Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications" (2013). Theses and Dissertations. 908. http://scholarworks.uark.edu/etd/908 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications Design, Development, and Characterization of Novel Antimicrobial Peptides for Pharmaceutical Applications A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Cell and Molecular Biology by Yazan H. Akkam Jordan University of Science and Technology Bachelor of Science in Pharmacy, 2001 Al-Balqa Applied University Master of Science in Biochemistry and Chemistry of Pharmaceuticals, 2005 August 2013 University of Arkansas This dissertation is approved for recommendation to the Graduate Council. Dr. David S. McNabb Dissertation Director Professor Roger E. Koeppe II Professor Gisela F. Erf Committee Member Committee Member Professor Ralph L. Henry Dr. Suresh K. Thallapuranam Committee Member Committee Member ABSTRACT Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs.
    [Show full text]
  • Antimicrobial Peptides in Reptiles
    Pharmaceuticals 2014, 7, 723-753; doi:10.3390/ph7060723 OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review Antimicrobial Peptides in Reptiles Monique L. van Hoek National Center for Biodefense and Infectious Diseases, and School of Systems Biology, George Mason University, MS1H8, 10910 University Blvd, Manassas, VA 20110, USA; E-Mail: [email protected]; Tel.: +1-703-993-4273; Fax: +1-703-993-7019. Received: 6 March 2014; in revised form: 9 May 2014 / Accepted: 12 May 2014 / Published: 10 June 2014 Abstract: Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development.
    [Show full text]
  • Analysis of the Solution Structure of the Human Antibiotic Peptide Dermcidin and Its Interaction with Phospholipid Vesicles
    BMB reports Analysis of the solution structure of the human antibiotic peptide dermcidin and its interaction with phospholipid vesicles Hyun Ho Jung1, Sung-Tae Yang2, Ji-Yeong Sim1, Seungkyu Lee1, Ju Yeon Lee1, Ha Hyung Kim3, Song Yub Shin4 & Jae Il Kim1,* 1Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 2Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, 3College of Pharmacy, Chung-Ang University, Seoul, 4Department of Bio-Materials, Graduate School and Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju 501-759, Korea Dermcidin is a human antibiotic peptide that is secreted by the of the modes of action of various antimicrobial peptides have sweat glands and has no homology to other known antimicro- revealed that their cationic nature contributes to their initial bial peptides. As an initial step toward understanding dermci- binding to negatively charged bacterial membranes through din’s mode of action at bacterial membranes, we used homo- electrostatic interaction, while their amphipathic structures en- nuclear and heteronuclear NMR to determine the conforma- hance peptide-lipid interactions at the water-bilayer interface, tion of the peptide in 50% trifluoroethanol solution. We found ultimately leading to cell death via pore formation or mem- that dermcidin adopts a flexible amphipathic α-helical struc- brane disintergration (9-14). ture with a helix-hinge-helix motif, which is a common molec- Dermcidin (DCD) is an antimicrobial peptide found in hu- ular fold among antimicrobial peptides. Spin-down assays of man sweat.
    [Show full text]
  • Activity by Specific Inhibition of Myeloperoxidase Hlf1-11 Exerts Immunomodulatory Effects the Human Lactoferrin-Derived Peptide
    The Human Lactoferrin-Derived Peptide hLF1-11 Exerts Immunomodulatory Effects by Specific Inhibition of Myeloperoxidase Activity This information is current as of September 25, 2021. Anne M. van der Does, Paul J. Hensbergen, Sylvia J. Bogaards, Medine Cansoy, André M. Deelder, Hans C. van Leeuwen, Jan W. Drijfhout, Jaap T. van Dissel and Peter H. Nibbering J Immunol 2012; 188:5012-5019; Prepublished online 20 Downloaded from April 2012; doi: 10.4049/jimmunol.1102777 http://www.jimmunol.org/content/188/10/5012 http://www.jimmunol.org/ References This article cites 39 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/188/10/5012.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 25, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The Human Lactoferrin-Derived Peptide hLF1-11 Exerts Immunomodulatory Effects by Specific Inhibition of Myeloperoxidase Activity Anne M.
    [Show full text]