title: Peptides with dual mode of action: Killing bacteria and preventing endotoxin-induced sepsis.
abstract: Bacterial infections, with the most severe form being sepsis, can often not be treated adequately leading to high morbidity and lethality of infected patients in critical care units. In particular, the increase in resistant bacterial strains and the lack of new antibiotics are main reasons for the worsening of the current situation, As a new approach, the use of antimicrobial peptides (AMPs) seems to be promising, combining the ability of broad-spectrum bactericidal activity and low potential of induction of resistance. Peptides based on natural defense proteins or polypeptides such as lactoferrin, Limulus anti-lipopolysaccharide factor (LALF), cathelicidins, and granulysins are candidates due to their high affinity to bacteria and to their pathogenicity factors, in first line lipopolysaccharide (LPS, endotoxin) of Gram-negative origin. In this review, we discuss literature with the focus on the use of AMPs from natural sources and their variants as antibacterial as well as anti-endotoxin (anti-inflammatory) drugs. Considerable progress has been made by the design of new AMPs for acting efficiently against the LPS-induced inflammation reaction in vitro as well as in vivo (mouse) models of sepsis. Furthermore, the data indicate that efficient antibacterial compounds are not necessarily equally efficient as anti-endotoxin drugs and vice versa. The most important reason for this may be the different molecular geometry of LPS in bacteria and in free form. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.
authors.affiliation: Forschungszentrum Borstel, Div. of Biophysics, Parkallee 10, D-23845 Borstel, Germany. Electronic address: kbrandenburg@fz-borstel.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: Clinical and Experimental Pathology, Parkallee 10, D-23845 Borstel, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Heinbockel
authors.affiliation: Forschungszentrum Borstel, Div. of Biophysics, Parkallee 10, D-23845 Borstel, Germany.
authors.forename: Wilmar
authors.initials: W
authors.lastname: Correa
authors.affiliation: Institute of Molecular Biosciences, Biophysics Division, University of Graz, NAWI Graz, BioTechMed Graz, Humboldtstr. 50/III, Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Lohner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; C075005:GNLY protein, human; D008070:Lipopolysaccharides; C034705:antilipopolysaccharide factor (Limulus); D007781:Lactoferrin
keywords: Antimicrobial peptides; Endotoxin; Inflammation; LPS-neutralization; Sepsis