Pairing Colicins B and E5 with Bdellovibrio bacteriovorus To Eradicate Carbapenem- and Colistin-Resistant Strains of Escherichia coli

Abstract

While diverse antibacterials are available in nature, each possesses their own strengths and limitations. One such antibacterial is colicins, proteinaceous toxins that are produced by strains of E. coli to subvert the growth or viability of other E. coli strains. Similarly, predatory bacteria, of which Bdellovibrio bacteriovorus is well-known, are microbes that actively predate on and consume other Gram-negative bacterial strains. While they are all quite active as antibacterials, they also present some limitations: rapid resistance development to colicins while predation does not completely kill their prey. Within this study, therefore, we evaluated the impact of two different colicins (colicin B [ColB] and colicin E5 [ColE5]) and B. bacteriovorus HD100 either individually or together against four clinical isolates of E. coli that are resistant to either colistin or carbapenem. While the ColB and ColE5 were quickly active when used alone, causing a significant loss in viability (>3-log) in susceptible populations after only 3 h, the pathogens always grew afterwards and had final cell densities that were similar with their respective controls. Predation with B. bacteriovorus HD100, in contrast, was most pronounced after 24 h (>3-log reduction in each pathogen viability but never complete). When combined, better killing efficiencies were observed with several of the pathogens, with complete eradication realized for two (<100 viable pathogens per mL). Given the diversity of colicins in nature and the broad-spectrum activities of B. bacteriovorus strains, the results presented here suggest there is a massive potential to control pathogens when they are used together.