New approaches in peptide antibiotics.

The emergence and rapid spread of extremely multiresistant bacteria necessitates every effort to develop novel antibacterial agents. Host-derived antimicrobial peptides (AMPs) pexiganan (a magainin), omiganan (an indolicidin), and iseganan (a protegrin) have been in clinical phases for more than 10 years and provide little in combating against those bacteria. Even though some recent approaches may yield more effective and better-tolerated derivatives of host-derived AMPs, most novel derivatives suffer from weak activity, nonspecific cytotoxicity, and apparent susceptibility to proteolysis. Few have undergone any systematic toxicity and efficacy studies. Bacterial peptides and their derivatives, such as lantibiotics, the RTA-3 peptide, and novel polymyxins, as well as certain peptidomimetics, such as ceragenins, might be more useful.

[1]  Jian Li,et al.  Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. , 2007, The Journal of antimicrobial chemotherapy.

[2]  A. Waring,et al.  Modular determinants of antimicrobial activity in platelet factor-4 family kinocidins. , 2007, Biochimica et biophysica acta.

[3]  Ronald N. Jones,et al.  Omiganan Pentahydrochloride (MBI 226), a Topical 12-Amino-Acid Cationic Peptide: Spectrum of Antimicrobial Activity and Measurements of Bactericidal Activity , 2004, Antimicrobial Agents and Chemotherapy.

[4]  E. Chapnick,et al.  Infectious Diseases: Parenteral Polymyxin B Use in Patients with Multidrug-Resistant Gram-Negative Bacteremia and Urinary Tract Infections: A Retrospective Case Series , 2008, The Annals of pharmacotherapy.

[5]  M. Dathe,et al.  Cyclization increases the antimicrobial activity and selectivity of arginine- and tryptophan-containing hexapeptides. , 2004, Biochemistry.

[6]  P. Iversen,et al.  Variations in Amino Acid Composition of Antisense Peptide-Phosphorodiamidate Morpholino Oligomer Affect Potency against Escherichia coli In Vitro and In Vivo , 2008, Antimicrobial Agents and Chemotherapy.

[7]  J. Shively,et al.  Neutrophil secondary necrosis is induced by LL‐37 derived from cathelicidin , 2008, Journal of leukocyte biology.

[8]  Olivier Taboureau,et al.  Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus , 2005, Nature.

[9]  L. Rice,et al.  The KQ Element, a Complex Genetic Region Conferring Transferable Resistance to Carbapenems, Aminoglycosides, and Fluoroquinolones in Klebsiella pneumoniae , 2008, Antimicrobial Agents and Chemotherapy.

[10]  W. Shi,et al.  Stability and Activity in Sputum of G10KHc, a Potent Anti‐Pseudomonas Antimicrobial Peptide , 2007, Chemical biology & drug design.

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

[12]  H. Nikaido,et al.  Molecular basis of bacterial outer membrane permeability. , 1985, Microbiological reviews.

[13]  C. Corbett,et al.  Comparative studies of the anti-leishmanial activity of three Crotalus durissus ssp. venoms , 2007, Parasitology Research.

[14]  M. Falagas,et al.  Toxicity of polymyxins: a systematic review of the evidence from old and recent studies , 2006, Critical care.

[15]  J. Kolls,et al.  Cytokine-mediated regulation of antimicrobial proteins , 2008, Nature Reviews Immunology.

[16]  K. Brown,et al.  The Host Defense Peptide LL-37 Selectively Permeabilizes Apoptotic Leukocytes , 2008, Antimicrobial Agents and Chemotherapy.

[17]  K. Yanagihara,et al.  Plectasin has antibacterial activity and no affect on cell viability or IL-8 production. , 2008, Biochemical and biophysical research communications.

[18]  M. Dathe,et al.  The interaction of arginine‐ and tryptophan‐rich cyclic hexapeptides with Escherichia coli membranes , 2008, Journal of peptide science : an official publication of the European Peptide Society.

[19]  Y. Ishitsuka,et al.  Amphiphilic poly(phenyleneethynylene)s can mimic antimicrobial peptide membrane disordering effect by membrane insertion. , 2006, Journal of the American Chemical Society.

[20]  T. Goldmann,et al.  Rationale for the Design of Shortened Derivatives of the NK-lysin-derived Antimicrobial Peptide NK-2 with Improved Activity against Gram-negative Pathogens* , 2007, Journal of Biological Chemistry.

[21]  R. Hancock,et al.  Antibacterial peptides for therapeutic use: obstacles and realistic outlook. , 2006, Current opinion in pharmacology.

[22]  N. Salzman.  Defensins versus bacteria: not just antibiotics anymore. , 2008, Gastroenterology.

[23]  R. Hancock,et al.  The roles of cathelicidin LL-37 in immune defences and novel clinical applications , 2009, Current opinion in hematology.

[24]  R. Hoffmann,et al.  Designer antibacterial peptides kill fluoroquinolone-resistant clinical isolates. , 2005, Journal of medicinal chemistry.

[25]  N. Woodford,et al.  Tackling antibiotic resistance: a dose of common antisense? , 2008, The Journal of antimicrobial chemotherapy.

[26]  B. Rasimick,et al.  Length Effects in Antimicrobial Peptides of the (RW)n Series , 2006, Antimicrobial Agents and Chemotherapy.

[27]  Ronald N. Jones,et al.  Antimicrobial activity of omiganan pentahydrochloride tested against contemporary bacterial pathogens commonly responsible for catheter-associated infections. , 2008, The Journal of antimicrobial chemotherapy.

[28]  Leif Smith,et al.  Therapeutic potential of type A (I) lantibiotics, a group of cationic peptide antibiotics. , 2008, Current opinion in microbiology.

[29]  Y. Arakawa,et al.  Nomenclature of Plasmid-Mediated 16S rRNA Methylases Responsible for Panaminoglycoside Resistance , 2008, Antimicrobial Agents and Chemotherapy.

[30]  D. Salunke,et al.  Design of a functionally equivalent nonglycosylated analog of the glycopeptide antibiotic formaecin I , 2006, Protein science : a publication of the Protein Society.

[31]  Anna Karlsson,et al.  Interleukin-8-Derived Peptide Has Antibacterial Activity , 2005, Antimicrobial Agents and Chemotherapy.

[32]  J. Wehkamp,et al.  Defensins and other antimicrobial peptides in inflammatory bowel disease , 2007, Current opinion in gastroenterology.

[33]  C. Dempsey,et al.  Origin of Low Mammalian Cell Toxicity in a Class of Highly Active Antimicrobial Amphipathic Helical Peptides* , 2008, Journal of Biological Chemistry.

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

[35]  Judy Halliday,et al.  Targeting the forgotten transglycosylases. , 2006, Biochemical pharmacology.

[36]  K. Tan,et al.  Inhibition of Gene Expression and Growth by Antisense Peptide Nucleic Acids in a Multiresistant β-Lactamase-Producing Klebsiella pneumoniae Strain , 2006, Antimicrobial Agents and Chemotherapy.

[37]  Jian He,et al.  Enhancement of Antimicrobial Activity against Pseudomonas aeruginosa by Coadministration of G10KHc and Tobramycin , 2006, Antimicrobial Agents and Chemotherapy.

[38]  J. Turnidge,et al.  Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. , 2006, The Lancet. Infectious diseases.

[39]  R. Nation,et al.  Antibiograms of multidrug-resistant clinical Acinetobacter baumannii: promising therapeutic options for treatment of infection with colistin-resistant strains. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  E. Bachère,et al.  Trypanocidal and leishmanicidal activities of different antimicrobial peptides (AMPs) isolated from aquatic animals. , 2008, Experimental parasitology.

[41]  M. Fridkin,et al.  The functional association of polymyxin B with bacterial lipopolysaccharide is stereospecific: studies on polymyxin B nonapeptide. , 2000, Biochemistry.

[42]  K. Aktories,et al.  Human alpha-defensins inhibit Clostridium difficile toxin B. , 2008, Gastroenterology.

[43]  M. Selsted,et al.  Microbicidal Properties and Cytocidal Selectivity of Rhesus Macaque Theta Defensins , 2007, Antimicrobial Agents and Chemotherapy.

[44]  Michael R. Yeaman,et al.  Unifying themes in host defence effector polypeptides , 2007, Nature Reviews Microbiology.

[45]  A. Mor,et al.  Antimicrobial peptide mimics for improved therapeutic properties. , 2009, Biochimica et biophysica acta.

[46]  M. Takano,et al.  Novel Polymyxin Derivatives Carrying Only Three Positive Charges Are Effective Antibacterial Agents , 2008, Antimicrobial Agents and Chemotherapy.

[47]  A. Waring,et al.  Structural correlates of antimicrobial efficacy in IL-8 and related human kinocidins. , 2007, Biochimica et biophysica acta.

[48]  W. Wu,et al.  Cathelicidin stimulates colonic mucus synthesis by up‐regulating MUC1 and MUC2 expression through a mitogen‐activated protein kinase pathway , 2008, Journal of cellular biochemistry.

[49]  P. Savage,et al.  Antimicrobial Activities of Ceragenins against Clinical Isolates of Resistant Staphylococcus aureus , 2007, Antimicrobial Agents and Chemotherapy.

[50]  T. Nguyen,et al.  Structural Correlates of Antibacterial and Membrane-Permeabilizing Activities in Acylpolyamines , 2006, Antimicrobial Agents and Chemotherapy.

[51]  Ayyalusamy Ramamoorthy,et al.  Deletion of all cysteines in tachyplesin I abolishes hemolytic activity and retains antimicrobial activity and lipopolysaccharide selective binding. , 2006, Biochemistry.

[52]  G. Zhanel,et al.  Antibacterial Activity of Ultrashort Cationic Lipo-β-Peptides , 2009, Antimicrobial Agents and Chemotherapy.

[53]  Gregory N Tew,et al.  De novo designed synthetic mimics of antimicrobial peptides. , 2008, Current opinion in biotechnology.

[54]  S. Fournel,et al.  Mimicking helical antibacterial peptides with nonpeptidic folding oligomers. , 2006, Chemistry & biology.

[55]  R. Hancock,et al.  Peptide Antimicrobial Agents , 2006, Clinical Microbiology Reviews.

[56]  Guang Yang,et al.  Glycopeptides: Update on an old successful antibiotic class. , 2006, Biochemical pharmacology.

[57]  Amit Kumar,et al.  Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups. , 2007, Biomacromolecules.

[58]  K. Hahm,et al.  Cathelicidin‐derived Trp/Pro‐rich antimicrobial peptides with lysine peptoid residue (Nlys): therapeutic index and plausible mode of action , 2007, Journal of peptide science : an official publication of the European Peptide Society.

[59]  P. Janmey,et al.  Resistance of the antibacterial agent ceragenin CSA-13 to inactivation by DNA or F-actin and its activity in cystic fibrosis sputum. , 2007, The Journal of antimicrobial chemotherapy.

[60]  W. DeGrado,et al.  De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers , 2009, Proceedings of the National Academy of Sciences.

[61]  H. Sahl,et al.  The co-evolution of host cationic antimicrobial peptides and microbial resistance , 2006, Nature Reviews Microbiology.

[62]  C. Ricci,et al.  Antimicrobial Activity of Novel Dendrimeric Peptides Obtained by Phage Display Selection and Rational Modification , 2005, Antimicrobial Agents and Chemotherapy.

[63]  M. Vaara.  Increased outer membrane resistance to ethylenediaminetetraacetate and cations in novel lipid A mutants , 1981, Journal of bacteriology.

[64]  Ronald N. Jones,et al.  Antimicrobial Activity of Omiganan Pentahydrochloride against Contemporary Fungal Pathogens Responsible for Catheter-Associated Infections , 2008, Antimicrobial Agents and Chemotherapy.

[65]  A. Norrby-Teglund,et al.  Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans , 2008, Infection and Immunity.

[66]  Wuyuan Lu,et al.  Induction of group A Streptococcus virulence by a human antimicrobial peptide , 2008, Proceedings of the National Academy of Sciences.

[67]  Ronald N. Jones,et al.  Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa. , 2007, The Journal of antimicrobial chemotherapy.

[68]  M. M. Keber,et al.  Combination of Antimicrobial and Endotoxin-Neutralizing Activities of Novel Oleoylamines , 2005, Antimicrobial Agents and Chemotherapy.