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Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii

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Abstract

Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD0, LD50, LD100). Protective dose 50 (PD50) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD0. The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1–8)M(1–18) was the less haemolytic on mouse erythrocytes. LD0 (mg/kg) was 32 for CA(1–8)M(1–18), CA(1–7)M(2–9), and Oct-CA(1–7)M(2–9), and 16 for CA(1–7)M(5–9). PD50 was not achieved with non-toxic doses (≤LD0). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration (p < 0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii.

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Acknowledgement

This work was supported by the Spanish Ministry of Science and Innovation (grant PET2006-0139 to D.A. and L.R.), and by the Spanish Ministry of Health (Fondo de Investigaciones Sanitarias-FEDER, grants PI061125 and PI040827 to L.R., PI040885 to D.A., PI041854 to J.A.B. and PI040624 to J.P.) Additional funding from the regional governments of Madrid (S-BIO-0260/2006 to L.R.) and Catalonia (SGR2005-00494 to D.A.) is acknowledged. L.R. belongs to the COMBACT Network (BIO260) (Comunidad Autónoma de Madrid). J.P. belongs to the Spanish Network for Research in Infectious Diseases (REIPI RD06/0008), the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III-FEDER. CIBERES is an initiative from Instituto de Salud Carlos III.

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Authors and Affiliations

  1. Unidad Clínica de Enfermedades Infecciosas, Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/Universidad de Sevilla/CSIC Sevilla, 41013, Sevilla, Spain

    R. López-Rojas, F. Docobo-Pérez, M. E. Pachón-Ibáñez & J. Pachón

  2. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003, Barcelona, Spain

    B. G. de la Torre & D. Andreu

  3. Centro de Investigaciones Biológicas (CSIC), 28040, Madrid, Spain

    M. Fernández-Reyes & L. Rivas

  4. Fundación Caubet-CIMERA Illes Balears and Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CibeRes), 07110, Bunyola, Spain

    C. March & J. A. Bengoechea

  5. Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain

    R. López-Rojas

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  1. R. López-Rojas
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  8. D. Andreu
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  10. J. Pachón
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Correspondence to R. López-Rojas.

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López-Rojas, R., Docobo-Pérez, F., Pachón-Ibáñez, M.E. et al. Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii . Eur J Clin Microbiol Infect Dis 30, 1391–1398 (2011). https://doi.org/10.1007/s10096-011-1233-y

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