The Role of Antimicrobial Peptides in Preventing Multidrug-Resistant Bacterial Infections and Biofilm Formation

Over the last decade, decreasing effectiveness of conventional antimicrobial-drugs has caused serious problems due to the rapid emergence of multidrug-resistant pathogens. Furthermore, biofilms, which are microbial communities that cause serious chronic infections and dental plaque, form environments that enhance antimicrobial resistance. As a result, there is a continuous search to overcome or control such problems, which has resulted in antimicrobial peptides being considered as an alternative to conventional drugs. Antimicrobial peptides are ancient host defense effector molecules in living organisms. These peptides have been identified in diverse organisms and synthetically developed by using peptidomimic techniques. This review was conducted to demonstrate the mode of action by which antimicrobial peptides combat multidrug-resistant bacteria and prevent biofilm formation and to introduce clinical uses of these compounds for chronic disease, medical devices, and oral health. In addition, combinations of antimicrobial peptides and conventional drugs were considered due to their synergetic effects and low cost for therapeutic treatment.

[1]  B. Bassler,et al.  Quorum sensing: cell-to-cell communication in bacteria. , 2005, Annual review of cell and developmental biology.

[2]  H. G. Boman,et al.  Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine , 1993, Infection and immunity.

[3]  Peng Li,et al.  Perturbation of Lipopolysaccharide (LPS) Micelles by Sushi 3 (S3) Antimicrobial Peptide , 2004, Journal of Biological Chemistry.

[4]  W. Kamysz,et al.  In vitro activity and killing effect of the synthetic hybrid cecropin A-melittin peptide CA(1-7)M(2-9)NH(2) on methicillin-resistant nosocomial isolates of Staphylococcus aureus and interactions with clinically used antibiotics. , 2004, Diagnostic microbiology and infectious disease.

[5]  A. Mattick,et al.  Further observations on an inhibitory substance (nisin) from lactic streptococci. , 1947, Lancet.

[6]  Dudley H. Williams,et al.  A mass spectrometric assay for novel peptides: Application to Xenopus laevis skin secretions , 1985, Peptides.

[7]  Thomas Bjarnsholt,et al.  Antibiotic resistance of bacterial biofilms. , 2010, International journal of antimicrobial agents.

[8]  M. Zasloff Antimicrobial peptides of multicellular organisms , 2002, Nature.

[9]  A. Marchese,et al.  Activity of daptomycin on biofilms produced on a plastic support by Staphylococcus spp. , 2008, International journal of antimicrobial agents.

[10]  N Woodford,et al.  Vancomycin-resistant enterococci , 1993, The Lancet.

[11]  B. Brandsdal,et al.  Antimicrobial peptides with stability toward tryptic degradation. , 2008, Biochemistry.

[12]  David L. Smith,et al.  Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005 , 2007, Emerging infectious diseases.

[13]  A. Ramamoorthy,et al.  Structure, membrane orientation, mechanism, and function of pexiganan--a highly potent antimicrobial peptide designed from magainin. , 2009, Biochimica et biophysica acta.

[14]  D. Monroe Looking for Chinks in the Armor of Bacterial Biofilms , 2007, PLoS biology.

[15]  Y. Shai,et al.  Conjugation of a magainin analogue with lipophilic acids controls hydrophobicity, solution assembly, and cell selectivity. , 2002, Biochemistry.

[16]  G. Molle,et al.  Antibacterial activity and pore-forming properties of ceratotoxins: a mechanism of action based on the barrel stave model. , 2004, Biochimica et biophysica acta.

[17]  R. Hancock,et al.  Salt-Resistant Alpha-Helical Cationic Antimicrobial Peptides , 1999, Antimicrobial Agents and Chemotherapy.

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

[19]  G. Reid,et al.  Microbial Biofilms: Their Development and Significance for Medical Device—Related Infections , 1999, Journal of clinical pharmacology.

[20]  Ashok Kumar,et al.  Tumor necrosis factor-alpha induces functionally active hyaluronan-adhesive CD44 by activating sialidase through p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated human monocytic cells. , 2003, The Journal of biological chemistry.

[21]  B. Bonev,et al.  Molecular Mechanism of Target Recognition by Subtilin, a Class I Lanthionine Antibiotic , 2007, Antimicrobial Agents and Chemotherapy.

[22]  Anirban Bhunia,et al.  High-resolution solution structure of a designed peptide bound to lipopolysaccharide: transferred nuclear Overhauser effects, micelle selectivity, and anti-endotoxic activity. , 2007, Biochemistry.

[23]  C. Gardner,et al.  Hypothermia as an indicator of the acute effects of lipopolysaccharides : Comparison with serum levels of IL1β, IL6 and TNFα , 1996 .

[24]  Y. Carmeli,et al.  Improved antimicrobial peptides based on acyl-lysine oligomers , 2007, Nature Biotechnology.

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

[26]  J. Hansen,et al.  Nisin as a model food preservative. , 1994, Critical reviews in food science and nutrition.

[27]  Y. Shai,et al.  Mode of action of linear amphipathic alpha-helical antimicrobial peptides. , 1998, Biopolymers.

[28]  K. Yamauchi,et al.  Periodontitis, periodontopathic bacteria and lactoferrin , 2010, BioMetals.

[29]  A. Po,et al.  Ability of azlocillin and tobramycin in combination to delay or prevent resistance development in Pseudomonas aeruginosa. , 1999, The Journal of antimicrobial chemotherapy.

[30]  Robert E. W. Hancock,et al.  Multifunctional cationic host defence peptides and their clinical applications , 2011, Cellular and Molecular Life Sciences.

[31]  Jeffrey B. Kaplan,et al.  Differential Roles of Poly-N-Acetylglucosamine Surface Polysaccharide and Extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis Biofilms , 2007, Applied and Environmental Microbiology.

[32]  M. Zaiou Multifunctional antimicrobial peptides: therapeutic targets in several human diseases , 2007, Journal of Molecular Medicine.

[33]  Kyung-Soo Hahm,et al.  The membrane insertion of helical antimicrobial peptides from the N-terminus of Helicobacter pylori ribosomal protein L1. , 2010, Biochimica et biophysica acta.

[34]  N. Khardori,et al.  Biofilms in device-related infections , 1995, Journal of Industrial Microbiology.

[35]  D. Hultmark,et al.  Sequence and specificity of two antibacterial proteins involved in insect immunity , 1981, Nature.

[36]  K. Hahm,et al.  Cell selectivity and anti-inflammatory activity of a Leu/Lys-rich α-helical model antimicrobial peptide and its diastereomeric peptides , 2010, Peptides.

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

[38]  Krishna Kumar,et al.  Antimicrobial activity and protease stability of peptides containing fluorinated amino acids. , 2007, Journal of the American Chemical Society.

[39]  K. Leung,et al.  The effect of lactoferrin on oral bacterial attachment. , 2009, Oral microbiology and immunology.

[40]  N. Strynadka,et al.  Beta-lactam antibiotic resistance: a current structural perspective. , 2005, Current opinion in microbiology.

[41]  B. Pradines,et al.  Efflux mechanism, an attractive target to combat multidrug resistant Plasmodium falciparum and Pseudomonas aeruginosa. , 2009, Current medicinal chemistry.

[42]  R. Hancock,et al.  Antiendotoxin activity of cationic peptide antimicrobial agents , 1996, Infection and immunity.

[43]  Samuel I. Miller,et al.  Lipid A Acylation and Bacterial Resistance against Vertebrate Antimicrobial Peptides , 1998, Cell.

[44]  Kyung-Soo Hahm,et al.  Cell specificity, anti-inflammatory activity, and plausible bactericidal mechanism of designed Trp-rich model antimicrobial peptides. , 2009, Biochimica et biophysica acta.

[45]  T. Falla,et al.  Antimicrobial peptides: therapeutic potential , 2006, Expert opinion on pharmacotherapy.

[46]  Sanjay Saint,et al.  Guidelines for the prevention of intravascular catheter-related infections. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[47]  H. Vogel,et al.  Tryptophan- and arginine-rich antimicrobial peptides: structures and mechanisms of action. , 2006, Biochimica et biophysica acta.

[48]  R. Hancock,et al.  Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies , 2006, Nature Biotechnology.

[49]  D. Cvitkovitch,et al.  Quorum sensing in streptococcal biofilm formation. , 2005, Trends in microbiology.

[50]  Y. Shai,et al.  From “carpet” mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides , 2001, Peptides.

[51]  C. Hernández-Chico,et al.  The peptide antibiotic microcin B17 induces double‐strand cleavage of DNA mediated by E. coli DNA gyrase. , 1991, The EMBO journal.

[52]  P. Marsh Dental plaque: biological significance of a biofilm and community life-style. , 2005, Journal of clinical periodontology.

[53]  J. Bang,et al.  Antimicrobial specificity and mechanism of action of disulfide-removed linear analogs of the plant-derived Cys-rich antimicrobial peptide Ib-AMP1 , 2009, Peptides.

[54]  Themis Lazaridis,et al.  Antimicrobial peptides in toroidal and cylindrical pores. , 2010, Biochimica et biophysica acta.

[55]  M. Ghadiri,et al.  Systemic Antibacterial Activity of Novel Synthetic Cyclic Peptides , 2005, Antimicrobial Agents and Chemotherapy.

[56]  D. White,et al.  Microbiota of Plaque Microcosm Biofilms: Effect of Three Times Daily Sucrose Pulses in Different Simulated Oral Environments , 2007, Caries Research.

[57]  N. Strynadka,et al.  β-Lactam antibiotic resistance: a current structural perspective , 2005 .

[58]  K. Brogden Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? , 2005, Nature Reviews Microbiology.

[59]  D. Hassett,et al.  Modulation of lung epithelial functions by Pseudomonas aeruginosa. , 2005, Trends in microbiology.

[60]  G. Jung,et al.  Epidermin: sequencing of a heterodetic tetracyclic 21-peptide amide antibiotic. , 1986, European journal of biochemistry.

[61]  E. Breukink,et al.  Membrane permeabilization by multivalent anti-microbial peptides. , 2009, Protein and peptide letters.

[62]  M. Zasloff,et al.  Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[63]  L. Yang,et al.  Barrel-stave model or toroidal model? A case study on melittin pores. , 2001, Biophysical journal.

[64]  B. Berger-Bächi,et al.  Factors influencing methicillin resistance in staphylococci , 2002, Archives of Microbiology.

[65]  R. Hancock,et al.  Biological properties of structurally related alpha-helical cationic antimicrobial peptides. , 1999, Infection and immunity.

[66]  Y. Shai,et al.  Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. , 1996, Journal of molecular biology.

[67]  Samuel I. Miller,et al.  How intracellular bacteria survive: surface modifications that promote resistance to host innate immune responses. , 1999, The Journal of infectious diseases.

[68]  D. Cardo,et al.  Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002 , 2007, Public health reports.

[69]  Michael R. Yeaman,et al.  Mechanisms of Antimicrobial Peptide Action and Resistance , 2003, Pharmacological Reviews.

[70]  J. Nickel,et al.  Bacterial biofilms: influence on the pathogenesis, diagnosis and treatment of urinary tract infections. , 1994, The Journal of antimicrobial chemotherapy.

[71]  N. Sharon,et al.  Binding of simple carbohydrates and some N-acetyllactosamine-containing oligosaccharides to Erythrina cristagalli agglutinin as followed with a fluorescent indicator ligand. , 1984, Archives of biochemistry and biophysics.

[72]  P. Sankaridurg,et al.  In vivo performance of melimine as an antimicrobial coating for contact lenses in models of CLARE and CLPU. , 2009, Investigative ophthalmology & visual science.

[73]  B. Iglewski,et al.  P. aeruginosa Biofilms in CF Infection , 2008, Clinical reviews in allergy & immunology.

[74]  J. Łukasiak,et al.  Efficacy of Tachyplesin III, Colistin, and Imipenem against a Multiresistant Pseudomonas aeruginosa Strain , 2007, Antimicrobial Agents and Chemotherapy.

[75]  R. Hancock,et al.  Biological Properties of Structurally Related α-Helical Cationic Antimicrobial Peptides , 1999, Infection and Immunity.

[76]  Ralf Hoffmann,et al.  Identification of crucial residues for the antibacterial activity of the proline-rich peptide, pyrrhocoricin. , 2002, European journal of biochemistry.

[77]  Michael J. MacCoss,et al.  Aminoglycoside antibiotics induce bacterial biofilm formation , 2005, Nature.

[78]  Y. Porat,et al.  Acyl-Substituted Dermaseptin S4 Derivatives with Improved Bactericidal Properties, Including on Oral Microflora , 2006, Antimicrobial Agents and Chemotherapy.

[79]  I. Lasa,et al.  Cloning, Nucleotide Sequencing, and Analysis of the AcrAB-TolC Efflux Pump of Enterobacter cloacae and Determination of Its Involvement in Antibiotic Resistance in a Clinical Isolate , 2007, Antimicrobial Agents and Chemotherapy.

[80]  H. Dommisch,et al.  The immune response of oral epithelial cells induced by single-species and complex naturally formed biofilms. , 2009, Oral microbiology and immunology.

[81]  O. Kuipers,et al.  An Alternative Bactericidal Mechanism of Action for Lantibiotic Peptides That Target Lipid II , 2006, Science.

[82]  B. Beutler,et al.  Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: benefits and hazards of LPS hypersensitivity. , 2008, Immunobiology.

[83]  U. Seydel,et al.  Lipid-mediated resistance of Gram-negative bacteria against various pore-forming antimicrobial peptides , 2005, Journal of endotoxin research.

[84]  Simona Jevševar,et al.  PEGylation of therapeutic proteins , 2010, Biotechnology journal.

[85]  R. Proctor,et al.  In vitro susceptibility of Staphylococcus aureus to thrombin-induced platelet microbicidal protein-1 (tPMP-1) is influenced by cell membrane phospholipid composition and asymmetry. , 2007, Microbiology.

[86]  Paul Stoodley,et al.  Evolving concepts in biofilm infections , 2009, Cellular microbiology.

[87]  N. Kumar,et al.  A novel cationic‐peptide coating for the prevention of microbial colonization on contact lenses , 2008, Journal of applied microbiology.

[88]  C. Padilla,et al.  In vitro antimicrobial effect of bacteriocin PsVP-10 in combination with chlorhexidine and triclosan against Streptococcus mutans and Streptococcus sobrinus strains. , 2009, Archives of oral biology.

[89]  W. Kamysz,et al.  Potential Therapeutic Role of Cationic Peptides in Three Experimental Models of Septic Shock , 2002, Antimicrobial Agents and Chemotherapy.

[90]  Ashok Kumar,et al.  Tumor Necrosis Factor-α Induces Functionally Active Hyaluronan-adhesive CD44 by Activating Sialidase through p38 Mitogen-activated Protein Kinase in Lipopolysaccharide-stimulated Human Monocytic Cells* , 2003, Journal of Biological Chemistry.

[91]  J. Costerton,et al.  Antibiotic resistance of bacteria in biofilms , 2001, The Lancet.

[92]  H. Sahl,et al.  Biosynthesis and biological activities of lantibiotics with unique post-translational modifications. , 1995, European journal of biochemistry.

[93]  S. Lau,et al.  Mechanism of antibiotic efflux in Gram-negative bacteria. , 2003, Frontiers in bioscience : a journal and virtual library.

[94]  M. Phansalkar,et al.  Mersacidin, a new antibiotic from Bacillus. Fermentation, isolation, purification and chemical characterization. , 1992, The Journal of antibiotics.

[95]  Wei-Ting Huang,et al.  Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA , 2005, Nucleic acids research.

[96]  M. Falagas,et al.  Polymyxin B: similarities to and differences from colistin (polymyxin E) , 2007, Expert review of anti-infective therapy.

[97]  B. Ho,et al.  The Sushi peptides: structural characterization and mode of action against Gram-negative bacteria , 2008, Cellular and Molecular Life Sciences.

[98]  R. Kaptein,et al.  The nisin–lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics , 2004, Nature Structural &Molecular Biology.

[99]  T. Campbell,et al.  Antimicrobial Peptides for Plaque Control , 2009, Advances in dental research.

[100]  K. Yamauchi,et al.  Inhibitory Effects of Lactoferrin on Growth and Biofilm Formation of Porphyromonas gingivalis and Prevotella intermedia , 2009, Antimicrobial Agents and Chemotherapy.

[101]  Bonnie L Bassler,et al.  A strategy for antagonizing quorum sensing. , 2011, Molecular cell.

[102]  H. Sahl,et al.  Lantibiotics: mode of action, biosynthesis and bioengineering. , 2009, Current pharmaceutical biotechnology.

[103]  M. Yamazaki,et al.  Magainin 2-induced pore formation in the lipid membranes depends on its concentration in the membrane interface. , 2009, The journal of physical chemistry. B.

[104]  H. Sahl,et al.  Structural similarities of the staphylococcin-like peptide Pep-5 to the peptide antibiotic nisin , 1985, Antimicrobial Agents and Chemotherapy.

[105]  S J Ludtke,et al.  Membrane pores induced by magainin. , 1996, Biochemistry.

[106]  Duncan Patrick McGregor,et al.  Discovering and improving novel peptide therapeutics. , 2008, Current opinion in pharmacology.

[107]  H. Sahl,et al.  Mersacidin eradicates methicillin-resistant Staphylococcus aureus (MRSA) in a mouse rhinitis model. , 2004, The Journal of antimicrobial chemotherapy.

[108]  H. Sahl,et al.  The Lantibiotic Mersacidin Inhibits Peptidoglycan Synthesis by Targeting Lipid II , 1998, Antimicrobial Agents and Chemotherapy.

[109]  Y. Shai,et al.  Mode of action of linear amphipathic α-helical antimicrobial peptides , 1998 .

[110]  G. Thorne,et al.  Effects of daptomycin in combination with other antimicrobial agents: a review of in vitro and animal model studies. , 2009, The Journal of antimicrobial chemotherapy.

[111]  M. Nishida,et al.  Action mechanism of tachyplesin I and effects of PEGylation. , 2007, Biochimica et biophysica acta.

[112]  S. Gorman,et al.  Antimicrobial Activity of Short, Synthetic Cationic Lipopeptides , 2010, Chemical biology & drug design.

[113]  Pierre Nicolas,et al.  Multifunctional host defense peptides: intracellular‐targeting antimicrobial peptides , 2009, The FEBS journal.

[114]  H. H. Peter,et al.  Duramycins B and C, two new lanthionine containing antibiotics as inhibitors of phospholipase A2. Structural revision of duramycin and cinnamycin. , 1990, The Journal of antibiotics.

[115]  J. Kaplan Therapeutic Potential of Biofilm-Dispersing Enzymes , 2009 .

[116]  Seong-Cheol Park,et al.  C-terminal amidation of PMAP-23: translocation to the inner membrane of Gram-negative bacteria , 2010, Amino Acids.

[117]  K. Hahm,et al.  Antibacterial synergism of novel antibiotic peptides with chloramphenicol. , 2004, Biochemical and biophysical research communications.

[118]  A. Bayer,et al.  Inhibition of intracellular macromolecular synthesis in Staphylococcus aureus by thrombin-induced platelet microbicidal proteins. , 2002, The Journal of infectious diseases.

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

[120]  L. Wong,et al.  Oral Biofilms: Emerging Concepts in Microbial Ecology , 2010, Journal of dental research.

[121]  M. Yoshinari,et al.  Prevention of biofilm formation on titanium surfaces modified with conjugated molecules comprised of antimicrobial and titanium-binding peptides , 2010, Biofouling.

[122]  J. Carver,et al.  The solution structure and activity of caerin 1.1, an antimicrobial peptide from the Australian green tree frog, Litoria splendida. , 1997, European journal of biochemistry.

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

[124]  R. Isaacson MBI-226. Micrologix/Fujisawa. , 2003, Current opinion in investigational drugs.

[125]  L. Glaser Bacterial cell surface polysaccharides. , 1973, Annual review of biochemistry.

[126]  M. Nishida,et al.  Action mechanism of PEGylated magainin 2 analogue peptide. , 2007, Biochimica et biophysica acta.

[127]  T. Mogi,et al.  Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics , 2009, Cellular and Molecular Life Sciences.

[128]  S. Ludtke,et al.  Characterization of antibiotic peptide pores using cryo-EM and comparison to neutron scattering. , 2009, Biophysical journal.

[129]  Gianfranco Pasut,et al.  PEG conjugates in clinical development or use as anticancer agents: an overview. , 2009, Advanced drug delivery reviews.

[130]  Bruce A. Stanton,et al.  Pseudomonas aeruginosa biofilm formation in the cystic fibrosis airway. , 2008, Pulmonary pharmacology & therapeutics.

[131]  F. Veronese,et al.  The Impact of PEGylation on Biological Therapies , 2012, BioDrugs.

[132]  T. McIntosh,et al.  Melittin-induced bilayer leakage depends on lipid material properties: evidence for toroidal pores. , 2005, Biophysical journal.

[133]  S. Lovas,et al.  The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. , 2001, Biochemistry.

[134]  Dong-Kuk Lee,et al.  Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. , 2003, Biochemistry.

[135]  Paul Stoodley,et al.  The effect of the chemical, biological, and physical environment on quorum sensing in structured microbial communities , 2006, Analytical and bioanalytical chemistry.

[136]  S. Gellman,et al.  Mimicry of host-defense peptides by unnatural oligomers: antimicrobial beta-peptides. , 2002, Journal of the American Chemical Society.

[137]  J. Łukasiak,et al.  Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic antibiotics in the treatment of experimental staphylococcal catheter-related infection , 2006, Peptides.

[138]  J. Zimmerberg,et al.  Interaction of hagfish cathelicidin antimicrobial peptides with model lipid membranes , 2002, FEBS letters.

[139]  W. Stamm Catheter-associated urinary tract infections: epidemiology, pathogenesis, and prevention. , 1991, The American journal of medicine.

[140]  G. Duckworth,et al.  Surveillance and epidemiology of MRSA bacteraemia in the UK. , 2005, The Journal of antimicrobial chemotherapy.

[141]  Ayyalusamy Ramamoorthy,et al.  Cholesterol reduces pardaxin's dynamics-a barrel-stave mechanism of membrane disruption investigated by solid-state NMR. , 2010, Biochimica et biophysica acta.

[142]  Seong-Cheol Park,et al.  Synergism of Leu-Lys rich antimicrobial peptides and chloramphenicol against bacterial cells. , 2006, Biochimica et biophysica acta.

[143]  L. Kwak,et al.  Roles of antimicrobial peptides such as defensins in innate and adaptive immunity , 2003, Annals of the rheumatic diseases.

[144]  J W Costerton,et al.  The bacterial glycocalyx in nature and disease. , 1981, Annual review of microbiology.

[145]  S. Gellman,et al.  Mimicry of Host-Defense Peptides by Unnatural Oligomers: Antimicrobial β-Peptides , 2002 .

[146]  D. Whitcomb,et al.  Human Pancreatic Digestive Enzymes , 2007, Digestive Diseases and Sciences.

[147]  G. Seibert,et al.  Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity. , 1992, The Journal of antibiotics.

[148]  R. Darouiche,et al.  Antimicrobial and antibiofilm efficacy of triclosan and DispersinB combination. , 2009, The Journal of antimicrobial chemotherapy.

[149]  Paul Stoodley,et al.  Bacterial biofilms: from the Natural environment to infectious diseases , 2004, Nature Reviews Microbiology.

[150]  P. Henderson,et al.  Antibiotic resistance: multidrug efflux proteins, a common transport mechanism? , 2005, Natural product reports.

[151]  O. Brakstad,et al.  Mechanisms of methicillin resistance in staphylococci , 1997, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[152]  Mingyun Li,et al.  Bacterial interactions in dental biofilm , 2011, Virulence.

[153]  D. Sahal,et al.  Synergy with Rifampin and Kanamycin Enhances Potency, Kill Kinetics, and Selectivity of DeNovo-Designed Antimicrobial Peptides , 2010, Antimicrobial Agents and Chemotherapy.

[154]  R. D. McCormick,et al.  Guidelines for the prevention of intravascular catheter-related infections. , 2002, Infection control and hospital epidemiology.

[155]  C. B. Park,et al.  Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. , 1998, Biochemical and biophysical research communications.

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

[157]  S. Barriere Bacterial Resistance to β‐Lactams, and Its Prevention With Combination Antimicrobial Therapy , 1992, Pharmacotherapy.

[158]  S. Lovas,et al.  Interaction between heat shock proteins and antimicrobial peptides. , 2000, Biochemistry.

[159]  Zhimin Zhou,et al.  Lipid A modifications characteristic of Salmonella typhimurium are induced by NH4VO3 in Escherichia coli K12. Detection of 4-amino-4-deoxy-L-arabinose, phosphoethanolamine and palmitate. , 1999, The Journal of biological chemistry.

[160]  J S Brown,et al.  Oral biofilms, periodontitis and pulmonary infections. , 2007, Oral diseases.

[161]  R. Cantor Size distribution of barrel-stave aggregates of membrane peptides: influence of the bilayer lateral pressure profile. , 2002, Biophysical journal.

[162]  R. Titball,et al.  Proteolytic Degradation of Human Antimicrobial Peptide LL-37 by Bacillus anthracis May Contribute to Virulence , 2006, Antimicrobial Agents and Chemotherapy.

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

[164]  T. Algara,et al.  Antimicrobial and antifungal activities of a novel cationic antimicrobial peptide, omiganan, in experimental skin colonisation models. , 2009, International journal of antimicrobial agents.

[165]  C. Subbalakshmi,et al.  Mechanism of antimicrobial action of indolicidin. , 1998, FEMS microbiology letters.

[166]  K. Hojo,et al.  Bacterial Interactions in Dental Biofilm Development , 2009, Journal of dental research.

[167]  M. Gilmore,et al.  Quorum sensing and DNA release in bacterial biofilms. , 2006, Current opinion in microbiology.

[168]  V. Saba,et al.  Protective effects of the combination of alpha-helical antimicrobial peptides and rifampicin in three rat models of Pseudomonas aeruginosa infection. , 2008, The Journal of antimicrobial chemotherapy.

[169]  D. Storm,et al.  Polymyxin and related peptide antibiotics. , 1977, Annual review of biochemistry.

[170]  D. Kovacevich,et al.  Guidelines for the prevention of intravascular catheter-related infections: Centers for Disease Control and Prevention. , 2003, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[171]  B. Han,et al.  Modification of antimicrobial peptide with low molar mass poly(ethylene glycol). , 2008, Journal of biochemistry.

[172]  J. Palmer Bacterial Biofilms in Chronic Rhinosinusitis , 2006, The Annals of otology, rhinology & laryngology. Supplement.

[173]  Ju Hyun Cho,et al.  Buforins: histone H2A-derived antimicrobial peptides from toad stomach. , 2009, Biochimica et biophysica acta.

[174]  V. Nizet,et al.  ClpX Contributes to Innate Defense Peptide Resistance and Virulence Phenotypes of Bacillus anthracis , 2009, Journal of Innate Immunity.

[175]  Seong-Cheol Park,et al.  Amphipathic alpha-helical peptide, HP (2-20), and its analogues derived from Helicobacter pylori: pore formation mechanism in various lipid compositions. , 2008, Biochimica et biophysica acta.

[176]  J. Rudney Saliva and Dental Plaque , 2000, Advances in dental research.

[177]  Seong-Cheol Park,et al.  Antibiotic and synergistic effect of Leu-Lys rich peptide against antibiotic resistant microorganisms isolated from patients with cholelithiasis. , 2010, Biochemical and biophysical research communications.

[178]  D. Matthews,et al.  PROTEIN DIGESTION AND ABSORPTION , 1957 .

[179]  I. Sutherland Biofilm exopolysaccharides: a strong and sticky framework. , 2001, Microbiology.

[180]  Seong-Cheol Park,et al.  Investigation of toroidal pore and oligomerization by melittin using transmission electron microscopy. , 2006, Biochemical and biophysical research communications.

[181]  J. Costerton,et al.  Introduction to biofilm. , 1999, International journal of antimicrobial agents.

[182]  J. Grant Burgess,et al.  Molecular mechanisms of compounds affecting bacterial biofilm formation and dispersal , 2010, Applied Microbiology and Biotechnology.