Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains

  • P. Morici
  • W. Florio
  • C. Rizzato
  • E. Ghelardi
  • A. Tavanti
  • G. M. Rossolini
  • A. Lupetti
Original Article


The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1–11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1–11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1–11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1–11 and colistin are not strictly associated, and suggest an hLF1–11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1–11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.

Supplementary material

10096_2017_2987_MOESM1_ESM.docx (13 kb)
Table S1(DOCX 13 kb)
10096_2017_2987_MOESM2_ESM.docx (14 kb)
Table S2(DOCX 14 kb)


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© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Translational Research and of New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
  2. 2.NEST, Istituto Nanoscienze-CNR and Scuola Normale SuperiorePisaItaly
  3. 3.Department of BiologyUniversity of PisaPisaItaly
  4. 4.Department of Medical BiotechnologiesUniversity of SienaSienaItaly
  5. 5.Clinical Microbiology and Virology UnitFlorence Careggi University HospitalFlorenceItaly
  6. 6.Department of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
  7. 7.Don Carlo Gnocchi FoundationFlorenceItaly

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