JAC Advance Access originally published online on April 24, 2006
Journal of Antimicrobial Chemotherapy 2006 58(1):95-100; doi:10.1093/jac/dkl145
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Studies on the antimicrobial activity of cecropin A–melittin hybrid peptides in colistin-resistant clinical isolates of Acinetobacter baumannii
1 Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío Avda. Manuel Siurot s/n, 41013 Sevilla, Spain; 2 Service of Emergency and Critical Care, Hospitales Universitarios Virgen del Rocío Avda. Manuel Siurot s/n, 41013 Sevilla, Spain 3 Centro de Investigaciones Biológicas (CSIC), C/ Ramiro de Maeztu 9 28040 Madrid, 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
Received 27 October 2005; returned 17 February 2006; revised 9 March 2006; accepted 27 March 2006
*Corresponding author. Tel/Fax: +34-955012376; E-mail: jeronimopachon{at}telefonica.net
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
-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