Human cathelicidin LL-37 prevents bacterial biofilm formation.

Human pathogens often colonize their host by the formation of biofilms. These surface-attached aggregates of bacteria are characterized by a self-produced extracellular matrix, which makes them highly resistant towards antibiotic treatment. Their abilities to adhere to abiotic surfaces (e.g., catheters and other medical devices) also makes bacterial biofilm formation a challenge in modern medicine. Antimicrobial peptides have lately been introduced as a potential class of drug molecules for combating severe hospital-acquired infections. One of these peptides, human cathelicidin LL-37, has recently been demonstrated to bridge innate and adaptive host defence, in addition to facilitating a robust antibiofilm effect at sub-inhibitory concentrations. In this review we will discuss the evidence, potential and challenges for LL-37 as a candidate molecule for therapeutic use.

[1]  R. Shaykhiev,et al.  Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[2]  D. Bailey,et al.  Mucociliary clearance in patients with cystic fibrosis and in normal subjects. , 1994, American journal of respiratory and critical care medicine.

[3]  Göran Carlsson,et al.  Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study , 2002, The Lancet.

[4]  J. Palmblad,et al.  Kostmann syndrome or infantile genetic agranulocytosis, part one: Celebrating 50 years of clinical and basic research on severe congenital neutropenia , 2006, Acta paediatrica.

[5]  David J. Arenillas,et al.  Systems biology evaluation of immune responses induced by human host defence peptide LL-37 in mononuclear cells. , 2009, Molecular bioSystems.

[6]  M. Kagnoff,et al.  Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. , 2003, Gastroenterology.

[7]  C. Cho,et al.  Effects of cathelicidin and its fragments on three key enzymes of HIV-1 , 2011, Peptides.

[8]  M. Urashima,et al.  Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. , 2010, The American journal of clinical nutrition.

[9]  R. Hancock,et al.  Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and impact on treatment. , 2000, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[10]  Robert E. W. Hancock,et al.  The Cationic Antimicrobial Peptide LL-37 Modulates Dendritic Cell Differentiation and Dendritic Cell-Induced T Cell Polarization1 , 2004, The Journal of Immunology.

[11]  G. Menexes,et al.  Salivary concentration of the antimicrobial peptide LL-37 in children. , 2012, Archives of oral biology.

[12]  S. Chae,et al.  Expression of cathelicidin in human salivary glands. , 2003, Archives of otolaryngology--head & neck surgery.

[13]  K V Chace,et al.  Comparison of physicochemical properties of purified mucus glycoproteins isolated from respiratory secretions of cystic fibrosis and asthmatic patients. , 1985, Biochemistry.

[14]  Guangshun Wang,et al.  Anti-Human Immunodeficiency Virus Type 1 Activities of Antimicrobial Peptides Derived from Human and Bovine Cathelicidins , 2008, Antimicrobial Agents and Chemotherapy.

[15]  C. Prigent-Combaret,et al.  Developmental pathway for biofilm formation in curli-producing Escherichia coli strains: role of flagella, curli and colanic acid. , 2000, Environmental microbiology.

[16]  Nikolaus Blin,et al.  Dermcidin: a novel human antibiotic peptide secreted by sweat glands , 2001, Nature Immunology.

[17]  Nicholas W. Kin,et al.  Cathelin‐related antimicrobial peptide differentially regulates T‐ and B‐cell function , 2011, European journal of immunology.

[18]  P. Marsh,et al.  Dental plaque as a biofilm , 1995, Journal of Industrial Microbiology.

[19]  R. Hancock,et al.  Structure-based design of an indolicidin peptide analogue with increased protease stability. , 2003, Biochemistry.

[20]  R. Lehrer,et al.  Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epithelium. , 2000, Oral microbiology and immunology.

[21]  M. Benincasa,et al.  Activity of antimicrobial peptides in the presence of polysaccharides produced by pulmonary pathogens , 2009, Journal of peptide science : an official publication of the European Peptide Society.

[22]  H. Jenssen,et al.  Antimicrobial β‐Peptides and α‐Peptoids , 2011, Chemical biology & drug design.

[23]  Richard C Boucher,et al.  Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. , 2002, The Journal of clinical investigation.

[24]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[25]  R. Hancock,et al.  Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation , 2008, Infection and Immunity.

[26]  Guangshun Wang,et al.  Structure, dynamics, and antimicrobial and immune modulatory activities of human LL-23 and its single-residue variants mutated on the basis of homologous primate cathelicidins. , 2012, Biochemistry.

[27]  G. Emingil,et al.  Antimicrobial peptide hCAP-18/LL-37 protein and mRNA expressions in different periodontal diseases. , 2011, Oral diseases.

[28]  M. Campa,et al.  Use of antimicrobial peptides against microbial biofilms: advantages and limits. , 2011, Current medicinal chemistry.

[29]  H. Jörnvall,et al.  The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. , 2000, Blood.

[30]  Biju Jacob,et al.  An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[31]  D. Sack,et al.  Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[32]  C. Ross,et al.  Regulation of Cathelicidin Gene Expression: Induction by Lipopolysaccharide, Interleukin-6, Retinoic Acid, andSalmonella enterica Serovar Typhimurium Infection , 2000, Infection and Immunity.

[33]  C. Roques,et al.  Fusobacterium nucleatum in periodontal health and disease. , 2011, Current issues in molecular biology.

[34]  R. Gallo,et al.  Anti-fungal activity of cathelicidins and their potential role in Candida albicans skin infection. , 2005, The Journal of investigative dermatology.

[35]  N. Høiby,et al.  Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients , 2009, Pediatric pulmonology.

[36]  R. Gallo,et al.  Structure-Function Relationships among Human Cathelicidin Peptides: Dissociation of Antimicrobial Properties from Host Immunostimulatory Activities , 2005, The Journal of Immunology.

[37]  R. Hancock,et al.  New insights into cathelicidin modulation of adaptive immunity , 2011, European journal of immunology.

[38]  S. Molin,et al.  The clinical impact of bacterial biofilms , 2011, International Journal of Oral Science.

[39]  V. Korolik,et al.  Inhibition of Bacterial Biofilm Formation and Swarming Motility by a Small Synthetic Cationic Peptide , 2012, Antimicrobial Agents and Chemotherapy.

[40]  M. Otto,et al.  Staphylococcus epidermidis infections. , 2002, Microbes and infection.

[41]  R. Kolter,et al.  Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development , 1998, Molecular microbiology.

[42]  M. Kuehn,et al.  Elicitation of Epithelial Cell-Derived Immune Effectors by Outer Membrane Vesicles of Nontypeable Haemophilus influenzae , 2011, Infection and Immunity.

[43]  R. Jurevic,et al.  Salivary Antimicrobial Peptide Expression and Dental Caries Experience in Children , 2005, Antimicrobial Agents and Chemotherapy.

[44]  R. Hancock,et al.  The Human Cationic Peptide LL-37 Induces Activation of the Extracellular Signal-Regulated Kinase and p38 Kinase Pathways in Primary Human Monocytes1 , 2004, The Journal of Immunology.

[45]  U. Römling,et al.  Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis , 2010, Letters in applied microbiology.

[46]  Kamran Ghaedi,et al.  Defensins: Antimicrobial Peptides of Innate Immunity , 2014 .

[47]  L. Tsui,et al.  Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. , 1989, Science.

[48]  S. Randell,et al.  Evidence for Periciliary Liquid Layer Depletion, Not Abnormal Ion Composition, in the Pathogenesis of Cystic Fibrosis Airways Disease , 1998, Cell.

[49]  B. Sandstedt,et al.  Antimicrobial protein hCAP18/LL‐37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells , 2005, International journal of cancer.

[50]  S. Chae,et al.  Expression of cathelicidin in recurrent throat infection. , 2006, International journal of pediatric otorhinolaryngology.

[51]  E. Dransfield,et al.  NaCl and sugar release, salivation and taste during mastication of salted chewing gum , 2003, Physiology & Behavior.

[52]  A. Waring,et al.  Evaluation of the Inactivation of Infectious Herpes Simplex Virus by Host-Defense Peptides , 2000, European Journal of Clinical Microbiology and Infectious Diseases.

[53]  K. Iwabuchi,et al.  A cathelicidin family of human antibacterial peptide LL‐37 induces mast cell chemotaxis , 2002, Immunology.

[54]  M. Wewers,et al.  A Novel P2X7 Receptor Activator, the Human Cathelicidin-Derived Peptide LL37, Induces IL-1β Processing and Release1 , 2004, The Journal of Immunology.

[55]  M. V. van Hoek,et al.  Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella. , 2010, Biochemical and biophysical research communications.

[56]  K. Berndt,et al.  Conformation-dependent Antibacterial Activity of the Naturally Occurring Human Peptide LL-37* , 1998, The Journal of Biological Chemistry.

[57]  Ling C. Huang,et al.  Multifunctional roles of human cathelicidin (LL-37) at the ocular surface. , 2006, Investigative ophthalmology & visual science.

[58]  M. Tollin,et al.  PU.1 and bacterial metabolites regulate the human gene CAMP encoding antimicrobial peptide LL-37 in colon epithelial cells. , 2008, Molecular immunology.

[59]  J. Odeberg,et al.  FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[60]  H. Jörnvall,et al.  Biochemical and antibacterial analysis of human wound and blister fluid. , 1996, European journal of biochemistry.

[61]  R. Bals,et al.  The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[62]  J. Schröder,et al.  A peptide antibiotic from human skin , 1997, Nature.

[63]  H. Lilja,et al.  The Human Cationic Antimicrobial Protein (hCAP-18) Is Expressed in the Epithelium of Human Epididymis, Is Present in Seminal Plasma at High Concentrations, and Is Attached to Spermatozoa , 2000, Infection and Immunity.

[64]  I. Shalit,et al.  All‐D‐magainin: chirality, antimicrobial activity and proteolytic resistance , 1990, FEBS letters.

[65]  K. Sayama,et al.  Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, {beta}-defensins and LL37, produced by human epithelial cells. , 2005, The Journal of antimicrobial chemotherapy.

[66]  I. Nagaoka,et al.  Evaluation of the effects of peptide antibiotics human β‐defensins‐1/‐2 and LL‐37 on histamine release and prostaglandin D2 production from mast cells , 2001 .

[67]  J. Calafat,et al.  Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. , 2001, Blood.

[68]  K. Hedlund,et al.  Uropathogenic Escherichia coli Modulates Immune Responses and Its Curli Fimbriae Interact with the Antimicrobial Peptide LL-37 , 2010, PLoS pathogens.

[69]  V. Nizet,et al.  Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. , 2001, The Journal of investigative dermatology.

[70]  Roland Contreras,et al.  Human Antimicrobial Peptides: Defensins, Cathelicidins and Histatins , 2005, Biotechnology Letters.

[71]  R. Gennaro,et al.  Antibacterial and anti-biofilm effects of cathelicidin peptides against pathogens isolated from cystic fibrosis patients , 2011, Peptides.

[72]  H. Wigzell,et al.  The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders* , 1997, The Journal of Biological Chemistry.

[73]  A. Johnsen,et al.  The Human Antibacterial Cathelicidin, hCAP-18, Is Bound to Lipoproteins in Plasma* , 1999, The Journal of Biological Chemistry.

[74]  B. Lee,et al.  Susceptibility of various oral bacteria to antimicrobial peptides and to phagocytosis by neutrophils. , 2007, Journal of periodontal research.

[75]  Arie V Nieuw Amerongen,et al.  Preparation of LL-37-grafted titanium surfaces with bactericidal activity. , 2006, Bioconjugate chemistry.

[76]  Michael Otto,et al.  Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system , 2004, Cellular microbiology.

[77]  A. Hovnanian,et al.  Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea , 2007, Nature Medicine.

[78]  C. Garbe,et al.  Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. , 2002, The Journal of investigative dermatology.

[79]  A. Johnsen,et al.  hCAP‐18, a cathelin/pro‐bactenecin‐like protein of human neutrophil specific granules , 1995, FEBS letters.

[80]  Takashi Shimizu,et al.  Sodium butyrate up-regulates cathelicidin gene expression via activator protein-1 and histone acetylation at the promoter region in a human lung epithelial cell line, EBC-1. , 2006, Molecular immunology.

[81]  J. Malm,et al.  Isolation of human cationic antimicrobial protein-18 from seminal plasma and its association with prostasomes. , 2002, Human reproduction.

[82]  Scott N. Dean,et al.  Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus , 2011, BMC Microbiology.

[83]  John H. White,et al.  Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression1 , 2004, The Journal of Immunology.

[84]  U. Francke,et al.  Structural, functional analysis and localization of the human CAP18 gene , 1996, FEBS letters.

[85]  Alessandro Tossi,et al.  Evolution of the Primate Cathelicidin , 2006, Journal of Biological Chemistry.

[86]  J. Larrick,et al.  Anti-microbial activity of human CAP18 peptides. , 1995, Immunotechnology : an international journal of immunological engineering.

[87]  Scott N. Dean,et al.  Susceptibility of Pseudomonas aeruginosa Biofilm to Alpha-Helical Peptides: D-enantiomer of LL-37 , 2011, Front. Microbio..

[88]  N. Høiby,et al.  Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis. , 1992, Thorax.

[89]  Y. Porat,et al.  In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria. , 2006, The Journal of antimicrobial chemotherapy.

[90]  J. Kaper,et al.  Synergistic role of curli and cellulose in cell adherence and biofilm formation of attaching and effacing Escherichia coli and identification of Fis as a negative regulator of curli. , 2009, Environmental microbiology.

[91]  H. Brismar,et al.  Staphylococcus epidermidis Isolated From Newborn Infants Express Pilus-Like Structures and Are Inhibited by the Cathelicidin-Derived Antimicrobial Peptide LL37 , 2009, Pediatric Research.

[92]  E. Greenberg,et al.  A component of innate immunity prevents bacterial biofilm development , 2002, Nature.

[93]  Henry Lin,et al.  The FASEB Journal • Research Communication Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin , 2022 .

[94]  M. Ståhle-Bäckdahl,et al.  The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. , 2003, The Journal of investigative dermatology.

[95]  P. DePetrillo,et al.  Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults , 2010, PloS one.

[96]  A. Kharazmi,et al.  Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth. , 2001, Microbes and infection.

[97]  Dong Young Kim,et al.  Antimicrobial Peptide LL-37 is Upregulated in Chronic Nasal Inflammatory Disease , 2003, Acta oto-laryngologica.

[98]  Domenico Romeo,et al.  Cathelicidins: a novel protein family with a common proregion and a variable C‐terminal antimicrobial domain , 1995, FEBS letters.

[99]  R. Bals,et al.  Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model. , 1999, The Journal of clinical investigation.

[100]  Alan J. Waring,et al.  Activities of LL-37, a Cathelin-Associated Antimicrobial Peptide of Human Neutrophils , 1998, Antimicrobial Agents and Chemotherapy.

[101]  Guangshun Wang,et al.  On-resin cleavage of bacterially expressed fusion proteins for purification of active recombinant peptides SK-29, KR-20, LL-29, and LL-23 from human sweat or skin. , 2007, Protein expression and purification.

[102]  C. Hart,et al.  Persistent and aggressive bacteria in the lungs of cystic fibrosis children. , 2002, British medical bulletin.

[103]  I. Nagaoka,et al.  Cathelicidin Family of Antibacterial Peptides CAP18 and CAP11 Inhibit the Expression of TNF-α by Blocking the Binding of LPS to CD14+ Cells1 , 2001, The Journal of Immunology.

[104]  Gerald B. Pier,et al.  Lung Infections Associated with Cystic Fibrosis , 2002, Clinical Microbiology Reviews.

[105]  J. Kreft,et al.  Microbial motility involvement in biofilm structure formation--a 3D modelling study. , 2007, Water science and technology : a journal of the International Association on Water Pollution Research.

[106]  Richard L. Gallo,et al.  Postsecretory Processing Generates Multiple Cathelicidins for Enhanced Topical Antimicrobial Defense1 , 2004, The Journal of Immunology.

[107]  A. Vitiello,et al.  Cutting Edge: Mast Cell Antimicrobial Activity Is Mediated by Expression of Cathelicidin Antimicrobial Peptide 1 , 2003, The Journal of Immunology.

[108]  H. Brismar,et al.  The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa , 2002, The British journal of dermatology.

[109]  J. Larrick,et al.  Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein , 1995, Infection and immunity.

[110]  James M. Wilson,et al.  Augmentation of Innate Host Defense by Expression of a Cathelicidin Antimicrobial Peptide , 1999, Infection and Immunity.

[111]  Guangshun Wang,et al.  Structures of Human Host Defense Cathelicidin LL-37 and Its Smallest Antimicrobial Peptide KR-12 in Lipid Micelles* , 2008, Journal of Biological Chemistry.

[112]  Celine Chan,et al.  Helix Induction in Antimicrobial Peptides by Alginate in Biofilms* , 2004, Journal of Biological Chemistry.

[113]  C. Camargo,et al.  Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[114]  D. Davidson,et al.  Antiviral Activity and Increased Host Defense against Influenza Infection Elicited by the Human Cathelicidin LL-37 , 2011, PloS one.

[115]  Takaaki Ohtake,et al.  Innate antimicrobial peptide protects the skin from invasive bacterial infection , 2001, Nature.

[116]  A. Veerman,et al.  Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Y. Shai,et al.  Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. , 1999, The Biochemical journal.

[118]  J. Odeberg,et al.  The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. , 1996, European journal of biochemistry.

[119]  A. Spormann,et al.  Antimicrobial Peptoids Are Effective against Pseudomonas aeruginosa Biofilms , 2011, Antimicrobial Agents and Chemotherapy.

[120]  M. Kagnoff,et al.  Cell Differentiation Is a Key Determinant of Cathelicidin LL-37/Human Cationic Antimicrobial Protein 18 Expression by Human Colon Epithelium , 2002, Infection and Immunity.

[121]  J. Malm,et al.  Processing of Seminal Plasma hCAP-18 to ALL-38 by Gastricsin , 2003, Journal of Biological Chemistry.

[122]  A. Scheynius,et al.  Antimicrobial Peptide LL‐37 Internalized by Immature Human Dendritic Cells Alters their Phenotype , 2006, Scandinavian journal of immunology.

[123]  H. Lührs,et al.  Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells. , 2004, Molecular immunology.

[124]  Ji Ming Wang,et al.  Ll-37, the Neutrophil Granule–And Epithelial Cell–Derived Cathelicidin, Utilizes Formyl Peptide Receptor–Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells , 2000, The Journal of experimental medicine.

[125]  D. Scaini,et al.  Primate cathelicidin orthologues display different structures and membrane interactions. , 2009, The Biochemical journal.

[126]  H. Flemming,et al.  The biofilm matrix , 2010, Nature Reviews Microbiology.

[127]  T. Hökfelt,et al.  The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection , 2006, Nature Medicine.

[128]  N. Høiby,et al.  Pseudomonas aeruginosa biofilms in cystic fibrosis. , 2010, Future microbiology.

[129]  J. van Marle,et al.  Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. , 2005, The Biochemical journal.

[130]  F. Virgilio,et al.  The Human Cathelicidin LL-37 Modulates the Activities of the P2X7 Receptor in a Structure-dependent Manner* , 2008, Journal of Biological Chemistry.

[131]  James F. Jones,et al.  Selective Killing of Vaccinia Virus by LL-37: Implications for Eczema Vaccinatum1 , 2004, The Journal of Immunology.

[132]  S. Naito,et al.  Curli Fibers Are Required for Development of Biofilm Architecture in Escherichia coli K‐12 and Enhance Bacterial Adherence to Human Uroepithelial Cells , 2005, Microbiology and immunology.

[133]  R. Lamont,et al.  Dental plaque formation. , 2000, Microbes and infection.

[134]  R. Larson,et al.  Effect of salt on the interactions of antimicrobial peptides with zwitterionic lipid bilayers. , 2006, Biochimica et biophysica acta.

[135]  Ling C. Huang,et al.  Human Cathelicidin (LL-37), a Multifunctional Peptide, is Expressed by Ocular Surface Epithelia and has Potent Antibacterial and Antiviral Activity , 2005, Current eye research.

[136]  M. Rossman,et al.  Role of curli fimbriae in mediating the cells of enterohaemorrhagic Escherichia coli to attach to abiotic surfaces , 2005, Journal of applied microbiology.

[137]  M. Welsh,et al.  Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis , 1993, Cell.

[138]  T. Ohtake,et al.  Cathelicidin Antimicrobial Peptides are Expressed in Salivary Glands and Saliva , 2002, Journal of dental research.

[139]  K. Lee,et al.  Effect of D-amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide. , 1999, Biochemical pharmacology.

[140]  J. Johansson,et al.  Apolipoprotein A-I Binds and Inhibits the Human Antibacterial/Cytotoxic Peptide LL-37* , 1998, The Journal of Biological Chemistry.

[141]  Ayyalusamy Ramamoorthy,et al.  LL-37, the only human member of the cathelicidin family of antimicrobial peptides. , 2006, Biochimica et biophysica acta.

[142]  D. Davidson,et al.  Impact of LL‐37 on anti‐infective immunity , 2005, Journal of leukocyte biology.

[143]  A. Barron,et al.  Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides , 2008, Proceedings of the National Academy of Sciences.

[144]  R. Rubin,et al.  Patient-reported outcomes in adults with type 2 diabetes using mealtime inhaled technosphere insulin and basal insulin versus premixed insulin. , 2011, Diabetes technology & therapeutics.