Synergistic activity profile of an antimicrobial peptide against multidrug-resistant and extensively drug-resistant strains of Gram-negative bacterial pathogens.
Infection sustained by multidrug-resistant and extensively drug-resistant bacterial pathogens is often untreatable with the standard of care antibiotics, and the combination of anti-infective compounds often represents the only therapeutic strategy to face this major clinical treat. SET-M33 is a novel antimicrobial peptide (AMP) that has demonstrated in vitro and in vivo antimicrobial activity against Gram-negative bacteria and has shown interesting features in preclinical evaluations. Particularly, it showed efficacy against a number of multidrug-resistant and extensively drug-resistant clinical strains of Gram-negative pathogens, in in vitro and in vivo assessments. Here, we explored the potential synergistic activity of SET-M33 in combination with different standard of care antibiotics by the checkerboard method against a panel of six strains of Gram-negative pathogens including multidrug-resistant and extensively drug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. SET-M33 showed synergistic activity with antibiotics of different families against these clinically relevant strains. A synergistic effect was observed for SET-M33 in combination with rifampin, meropenem, aztreonam, and tobramycin mostly on K. pneumoniae and A. baumannii strains, while the SET-M33 plus ciprofloxacin combination was additive with all tested strains. Synergy was not apparently linked to the bacterial species or phenotype but was rather strain-specific, highlighting the need for individual strain testing for synergistic antimicrobial combinations. These findings extend current knowledge on synergistic activity of AMPs in combination with conventional agents and support the potential role of SET-M33 as a novel therapeutic agent against antibiotic-resistant Gram-negative pathogens. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Department of Medical Biotechnologies, University of Siena, Siena, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Simona
http://orcid.org/0000-0003-3684-1891
S
Pollini
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Jlenia
http://orcid.org/0000-0001-8144-7186
J
Brunetti
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Samanta
S
Sennati
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|Clinical Microbiology and Virology Unit, Careggi University Hospital, Florence, Italy.|Don Carlo Gnocchi Foundation, Florence, Italy.
Gian Maria
http://orcid.org/0000-0002-9386-0434
GM
Rossolini
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Luisa
http://orcid.org/0000-0002-0738-5746
L
Bracci
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Alessandro
http://orcid.org/0000-0002-3832-8349
A
Pini
Department of Medical Biotechnologies, University of Siena, Siena, Italy.|Setlance srl, Siena, Italy.
Chiara
http://orcid.org/0000-0002-1027-8482
C
Falciani
D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
antimicrobial; antimicrobial synergy; bacteria resistances; branched; peptide