期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 52, 期 6, 页码 842-853出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2018.09.006
关键词
Antibiotic resistance; Antibiotic-phage therapy; Bacteriophage; Biofilm; Biofilm matrix degradation; Persister cell; Staggered combination
资金
- PRO-IMPLANT Foundation
Most antibiotics have limited or no activity against bacterial biofilms, whereas bacteriophages can eradicate biofilms. We evaluated whether Staphylococcus aureus - specific bacteriophage Sb-1 could eradicate biofilm, both alone and in combination with different classes of antibiotics, degrade the extracellular matrix and target persister cells. Biofilm of methicillin-resistant S. aureus (MRSA) ATCC 43300 was treated with Sb-1 alone or in (simultaneous or staggered) combination with fosfomycin, rifampin, vancomycin, daptomycin or ciprofloxacin. The matrix was visualized by confocal fluorescent microscopy. Persister cells were treated with 10 4 and 10(7) plaque-forming units (PFU)/mL Sb-1 for 3 h in phosphate-buffered saline (PBS), followed by colony-forming units (CFU) counting. Alternatively, bacteria were washed and incubated in fresh brain heart infusion (BHI) medium and bacterial growth assessed after a further 24 h. Pretreatment with Sb-1 followed by the administration of subinhibitory concentrations of antibiotic caused a synergistic effect in eradicating MRSA biofilm. Sb-1 determined a dose-dependent reduction of matrix exopolysaccharide. Sb-1 at 10(7) PFU/mL showed direct killing activity on approximate to 5x10(5) CFU/mL persisters. However, even a lower titer had lytic activity when phage-treated persister cells were inoculated in fresh medium, reverting to a normal-growing phenotype. This study provides valuable data on the enhancing effect of Sb-1 on antibiotic efficacy, exhibiting specific antibiofilm features. Sb-1 can degrade the MRSA polysaccharide matrix and target persister cells and is therefore suitable for treatment of biofilm-associated infections. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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