Coverage of diarrhoea‐associated Escherichia coli isolates from different origins with two types of phage cocktails

Abstract

Eighty-nine T4-like phages from our phage collection were tested against four collections of childhood diarrhoea-associated Escherichia coli isolates representing different geographical origins (Mexico versus Bangladesh), serotypes (69 O, 27 H serotypes), pathotypes (ETEC, EPEC, EIEC, EAEC, VTEC, Shigella), epidemiological settings (community and hospitalized diarrhoea) and years of isolation. With a cocktail consisting of 3 to 14 T4-like phages, we achieved 54% to 69% coverage against predominantly EPEC isolates from Mexico, 30% to 53% against mostly ETEC isolates from a prospective survey in Bangladesh, 24% to 61% against a mixture of pathotypes isolated from hospitalized children in Bangladesh, and 60% coverage against Shigella isolates. In comparison a commercial Russian phage cocktail containing a complex mixture of many different genera of coliphages showed 19%, 33%, 50% and 90% coverage, respectively, against the four above-mentioned collections. Few O serotype-specific phages and no broad-host range phages were detected in our T4-like phage collection. Interference phenomena between the phage isolates were observed when constituting larger phage cocktails. Since the coverage of a given T4-like phage cocktail differed with geographical area and epidemiological setting, a phage composition adapted to a local situation is needed for phage therapy approaches against E. coli pathogens.

Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo‐controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers

“…Loss of a virulence factor as phage receptor thus decreases the virulence of phage‐resistant bacteria, as previously observed in other phage‐pathogen systems (Smith and Huggins, Winstel et al ., ; Oechslin et al ., ). A phage therapy approach to target S. aureus is thus possible with a single phage – much unlike the high number of different phage types needed to target E. coli isolates, which frequently target lipopolysaccharides as bacterial receptors, an essential, but highly variable virulence factor (Chibani‐Chennoufi et al ., ; Tanji et al ., ; Bourdin et al ., ).…”

Absence of lysogeny in wild populations of Erwinia amylovora and Pantoea agglomerans

“…This mixture should minimize the risk of development of bacterial resistance and broaden the range of hosts controlled by the agent, as has been shown for phage cocktails against diarrhoea‐associated E. coli . (Bourdin et al ., ). Further optimization of the phage‐based biological would involve selection of phages for the cocktails based on host range studies and the selection of a carrier isolate of P. agglomerans that allows the production of high‐phage titres and secondary antimicrobial metabolites.…”

From bench to bed and back again: phage therapy of childhood Escherichia coli diarrhea

“…The T4‐like phages isolated on K‐12 showed a broader host range on E. coli pathogens. However, cocktails of at least 10 different T4‐like phage isolates were still needed to achieve a coverage of about 50% on large pathogen collections from Mexico and Bangladesh . When including more phage strains to increase the coverage, interference phenomena were encountered between the phages (operationally defined as a host range determined for a cocktail of phages, which is less broad than the sum of the host ranges determined for each phage tested individually) that prevented achieving higher coverage rates with more complex phage cocktails.…”