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2018 ; 11
(ä): 501-514
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Biofilm infections between Scylla and Charybdis: interplay of host antimicrobial
peptides and antibiotics
#MMPMID29674848
Chernysh S
; Gordya N
; Tulin D
; Yakovlev A
Infect Drug Resist
2018[]; 11
(ä): 501-514
PMID29674848
show ga
PURPOSE: The aim of this study is to improve the anti-biofilm activity of
antibiotics. We hypothesized that the antimicrobial peptide (AMP) complex of the
host's immune system can be used for this purpose and examined the assumption on
model biofilms. METHODS: FLIP7, the AMP complex of the blowfly Calliphora vicina
containing a combination of defensins, cecropins, diptericins and proline-rich
peptides was isolated from the hemolymph of bacteria-challenged maggots. The
complex interaction with antibiotics of various classes was studied in biofilm
and planktonic cultures of Staphylococcus aureus, Escherichia coli, Pseudomonas
aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by the checkerboard
method using trimethyl tetrazolium chloride cell viability and crystal violet
biofilm eradication assays supplemented with microscopic analysis. RESULTS: We
found that FLIP7 demonstrated: high synergy (fractional inhibitory concentration
index <0.25) with meropenem, amikacin, kanamycin, ampicillin, vancomycin and
cefotaxime; synergy with clindamycin, erythromycin and chloramphenicol; additive
interaction with oxacillin, tetracycline, ciprofloxacin and gentamicin; and no
interaction with polymyxin B. The interaction in planktonic cell models was
significantly weaker than in biofilms of the same strains. The analysis of the
dose-effect curves pointed to persister cells as a likely target of FLIP7
synergistic effect. The biofilm eradication assay showed that the effect also
caused total destruction of S. aureus and E. coli biofilm materials. The effect
allowed reducing the effective anti-biofilm concentration of the antibiotic to a
level well below the one clinically achievable (2-3 orders of magnitude in the
case of meropenem, ampicillin, cefotaxime and oxacillin). CONCLUSION: FLIP7 is a
highly efficient host antimicrobial system helping antibiotics to overcome
biofilm barriers through persisters' sensitization and biofilm material
destruction. It is promising for the treatment of biofilm infections as an
adjuvant of various small-molecule antibiotics.