Enhanced antibacterial effect of the novel T4-like bacteriophage KARL-1 in combination with antibiotics against multi-drug resistant Acinetobacter baumannii

摘要

The continuing rise of infections caused by multi-drug resistant bacteria has led to a renewed interest in bacteriophage therapy. Here we characterize phage vB_AbaM-KARL-1 with lytic activity against multi-drug resistant clinical isolates of Acinetobacter baumannii (AB). Besides genomic and phenotypic phage analysis, the objective of our study was to investigate the antibacterial outcome when the phage acts in concert with distinct antibiotics. KARL-1 belongs to the family of Myoviridae and is able to lyse 8 of 20 (40%) tested clinical isolates. Its double-stranded DNA genome consists of 166,560 bp encoding for 253 open reading frames. Genome wide comparison suggests that KARL-1 is a novel species within the subfamily Tevenvirinae, sharing 77% nucleotide identity (coverage 58%) with phage ZZ1. The antibacterial efficacy at various multiplicities of infection (MOI) was monitored either alone or in combination with meropenem, ciprofloxacin, and colistin. A complete clearance of liquid cultures was achieved with KARL-1 at an MOI of 10⁻¹ and meropenem (>128 mg/l). KARL-1 was still effective at an MOI of 10⁻⁷, but antibacterial activity was significantly augmented with meropenem. While ciprofloxacin did generally not support phage activity, the application of KARL-1 at an MOI of 10⁻⁷ and therapeutic doses of colistin significantly elevated bacterial suppression. Hence, KARL-1 represents a novel candidate for use against multi-drug resistant AB and the therapeutic outcome may be positively influenced by the addition of traditional antibiotics.