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dc.contributor.authorSaugar, José María-
dc.contributor.authorRodríguez-Hernández, María Jesús-
dc.contributor.authorDe la Torre, Beatriz G.-
dc.contributor.authorPachón-Ibáñez, M. E.-
dc.contributor.authorFernández-Reyes, María-
dc.contributor.authorAndreu, David-
dc.contributor.authorPachón, Jerónimo-
dc.contributor.authorRivas, Luis-
dc.identifier.citationAntimicrobial Agents and Chemotherapy 50: 1251- 1256 (2006)-
dc.description.abstractAcinetobacter baumannii has successfully developed resistance against all common antibiotics, including colistin (polymyxin E), the last universally active drug against this pathogen. The possible widespread distribution of colistin-resistant A baumannii strains may create an alarming clinical situation. In a previous work, we reported differences in lethal mechanisms between polymyxin B (PXB) and the cecropin A-melittin (CA-M) hybrid peptide CA(1-8)M(1-18) (KWKLFKKIGIGAVLKVLTTGLPALIS-NH2) on colistin-susceptible strains (J. M. Saugar, T. Alarcón, S. López-Hernández, M. López-Brea, D. Andreu, and L. Rivas, Antimicrob. Agents Chemother. 46:875-878, 2002). We now demonstrate that CA(1-8)M(1-18) and three short analogues, namely CA(1-7)M(2-9) (KWKLFKKIGAVLKVL-NH2), its Nα-octanoyl derivative (Oct-KWKLFKKIGAVLKVL-NH2), and CA(1-7)M(5-9) (KWKLLKKIGAVLKVL-NH 2) are active against two colistin-resistant clinical strains. In vitro, resistance to colistin sulfate was targeted to the outer membrane, as spheroplasts were equally lysed by a given peptide, regardless of their respective level of colistin resistance. The CA-M hybrids were more efficient than colistin in displacing lipopolysaccharide-bound dansyl-polymyxin B from colistin-resistant but not from colistin-susceptible strains. Similar improved performance of the CA-M hybrids in permeation of the inner membrane was observed, regardless of the resistance pattern of the strain. These results argue in favor of a possible use of CA-M peptides, and by extension other antimicrobial peptides with similar features, as alternative chemotherapy in colistin-resistant Acinetobacter infections. Copyright © 2006, American Society for Microbiology. All Rights Reserved.-
dc.description.sponsorshipSpanish Ministries of Education and Science (BIO2003-09056-CO2-02) and CSIC 200420F0332, the Spanish Network for Research in Infectious Diseases (ISCIII, C03/14), the Fondo de Investigacio´n Sanitaria (FIS PI04/0827, PI04/0624, and PI04/0885 to L.R., J.P., and D.A., respectively), and Consejerıa de Salud de la Junta de Andalucia (41/02) to J.P.-
dc.publisherAmerican Society for Microbiology-
dc.titleActivity of cecropin A-melittin hybrid peptides against colistin-resistant clinical strains of Acinetobacter baumannii: Molecular basis for the differential mechanisms of action-
dc.description.versionPeer Reviewed-
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