Skip Navigation



JAC Advance Access published online on April 24, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl145
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
58/1/95    most recent
dkl145v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Rodríguez-Hernández, M. J.
Right arrow Articles by Pachón, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodríguez-Hernández, M. J.
Right arrow Articles by Pachón, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received October 27, 2005
Revised March 9, 2006
Accepted March 27, 2006

Original article

Studies on the antimicrobial activity of cecropin A-melittin hybrid peptides in colistin-resistant clinical isolates of Acinetobacter baumannii

María Jesús Rodríguez-Hernández 1, José Saugar 2, Fernando Docobo-Pérez 3, Beatriz G. de la Torre 4, María Eugenia Pachón-Ibáñez 3, Andrés García-Curiel 5, Felipe Fernández-Cuenca 6, David Andreu 4, Luis Rivas 2, and Jerónimo Pachón 3 *

1 Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain; Service of Emergency and Critical Care, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
2 Centro de Investigaciones Biológicas (CSIC), C/ Ramiro de Maeztu 9, 28040 Madrid, Spain
3 Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
4 Departament of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr Aiguader 80, 08003 Barcelona, Spain
5 Service of Microbiology, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
6 Department of Microbiology, School of Medicine, University of Sevilla, Apdo. 914, 41080 Sevilla, Spain

* To whom correspondence should be addressed.
Jerónimo Pachón, E-mail: jeronimopachon{at}telefonica.net


  Abstract

Objectives: Acinetobacter baumannii has successfully developed resistance against all common antibiotics, including colistin, one of the last active drugs against this pathogen. We have tested whether the differences in lethal mechanism between polymyxin B and the cecropin A-melittin hybrid peptide CA(1-8)M(1-18), shown previously with a colistin-susceptible strain, can be exploited as a new chemotherapeutic alternative against colistin-resistant clinical isolates. Furthermore, the effect of capsule on the bactericidal activity of cecropin A-melittin analogues (CAMs) was tested.

Methods: MICs and MBCs of the four CAMs were determined for 13 clinical isolates. The bactericidal acti- vity of the antimicrobial peptides was measured using time-kill curves. The presence or absence of capsule was determined using Indian ink stain.

Results: The MIC ranges of CA(1-8)M(1-18) and three of its shortened analogues, namely CA(1-7)M(2-9), its N{alpha}-terminal octanoylated analogue and CA(1-7)M(5-9), for A. baumannii strains were 2-8, 2-4, 2-8 and 4-4 mg/L, respectively. MBCs differed by a factor of two at the most. All of the cecropin A-melittin peptides showed bactericidal activity in time-kill curves against four A. baumannii strains. The bactericidal activity of CAMs was not affected by the presence of capsule.

Conclusions: These results indicate that this class of peptides has a fast microbicidal effect on the colistin-resistant A. baumannii isolates, regardless of considerable structural variation among the four peptides and varying colistin MIC for the strains included in the study. Overall, the cecropin A-melittin peptides appear to be a promising alternative to overcome polymyxin resistance in A. baumannii.

Keywords: colistin resistance; A. baumannii; polymyxin; bactericidal activity; capsule.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.