Studies on the antimicrobial activity of cecropin A-melittin hybrid peptides in colistin-resistant clinical isolates of Acinetobacter baumannii.
OBJECTIVE
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 activity 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 Nalpha-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.
Rodríguez-Hernández
María Jesús
MJ
Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío Avda. Manuel Siurot s/n, 41013 Sevilla, Spain.
Saugar
José
J
Docobo-Pérez
Fernando
F
de la Torre
Beatriz G
BG
Pachón-Ibáñez
María Eugenia
ME
García-Curiel
Andrés
A
Fernández-Cuenca
Felipe
F
Andreu
David
D
Rivas
Luis
L
Pachón
Jerónimo
J
D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008555:Melitten / Q000737:chemistry / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology; D011994:Recombinant Proteins; D013997:Time Factors
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011113:Polymyxins; D011994:Recombinant Proteins; D008555:Melitten; C031161:cecropin A; D003091:Colistin