Abstract
During the antibiotic crisis, bacteriophages (briefly phages) are increasingly considered as potential antimicrobial pillars for the treatment of infectious diseases. Apart from acquired drug resistance, treatment options are additionally hampered by intrinsic, chromosomal-encoded resistance. For instance, the chromosomal ampC gene encoding for the AmpC-type β-lactamases is typically present in a number of nosocomial pathogens, including S. marcescens. In this study, phage SALSA (vB_SmaP-SALSA), with lytic activity against clinical isolates of S. marcescens, was isolated from effluent. Besides phage characterization, the aim of this study was to evaluate whether a synergistic effect between the antibiotic ampicillin/sulbactam (SAM) and phage can be achieved despite intrinsic drug resistance. Phage SALSA belongs to the Podoviridae family and genome-wide treeing analysis groups this phage within the phylogenetic radiation of T7-like viruses. The genome of Phage SALSA consists of 39,933 bp, which encode for 49 open reading frames. Phage SALSA was able to productively lyse 5 out of 20 clinical isolates (25%). A bacterial challenge with phage alone in liquid medium revealed that an initial strong bacterial decline was followed by bacterial re-growth, indicating the emergence of phage resistance. In contrast, the combination of SAM and phage, together at various concentrations, caused a complete bacterial eradication, confirmed by absorbance measurements and the absence of colony forming units after plating. The data show that it is principally possible to tackle the axiomatic condition of intrinsic drug resistance with a dual antimicrobial approach, which could be extended to other clinically relevant bacteria.
Highlights
In light of the inevitable spread of multi-drug resistance among clinically relevant bacterial species, new ways of antibacterial therapy are desperately needed
Recent studies have shown that the combined application of phages together with antibiotics leads to a stronger antibacterial activity than either substance alone, and reduces the chances for the occurrence of phage resistant variants [6]
A further differentiation of the isolates was possible via enterobacterial repetitive intergenic consensus PCR (ERIC-PCR), which ruled out the existence of duplicates (Supplementary Figure S1)
Summary
In light of the inevitable spread of multi-drug resistance among clinically relevant bacterial species, new ways of antibacterial therapy are desperately needed. This urgency has led to a reconsideration of the therapeutic use of bacteriophages (briefly: phages) [1,2,3]. Recent studies have shown that the combined application of phages together with antibiotics leads to a stronger antibacterial activity than either substance alone, and reduces the chances for the occurrence of phage resistant variants [6]. Synergistic interactions have been observed even with an antibiotic against which the targeted bacterial
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