Investigating the Use of Bacteriophages as New Decolonization Strategy for Intestinal Carriage of CTX-M-15-producing ST131 Escherichia coli: An In Vitro Continuous Culture System Model

Bernasconi, Odette J.; Campos-Madueno, Edgar I.; Donà, Valentina; Perreten, Vincent; Carattoli, Alessandra; Endimiani, Andrea (2020). Investigating the Use of Bacteriophages as New Decolonization Strategy for Intestinal Carriage of CTX-M-15-producing ST131 Escherichia coli: An In Vitro Continuous Culture System Model. Journal of global antimicrobial resistance, 22, pp. 664-671. Elsevier 10.1016/j.jgar.2020.05.018

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Objectives. We investigated the use of bacteriophages as a strategy to decolonize intestinal carriers of multidrug-resistant Escherichia coli. Methods. A fermentor was used as a continuous culture system for 48 hrs. Two different pools of feces (study I and II) obtained from volunteers were spiked with a CTX-M-15-producing ST131 E. coli (strain 4901.28) susceptible to bacteriophages and challenged with 3 doses of INTESTI Bacteriophage cocktail administered at 2, 6 and 10 hrs after inoculum. Bacterial typing was performed by implementing microdilution panels, spot test, rep-PCR, and whole-genome sequencing (including cgMLST and SNV analysis) obtained using both Nanopore and Illumina platforms. Results. In study I, bacteriophages decreased the numbers of 4901.28 dramatically (≤101 CFU/mL after 6 hrs). In contrast, during study II a phage-resistant mutant of 4901.28 persisted in the continuous culture (104 CFU/mL at 48 hrs). WGS revealed the presence of two additional plasmids in the mutant as well as 11 SNVs, including one chromosomal in a glycosyltransferase family 2 protein that is responsible for the transfer of sugars to polysaccharides and lipids. In both studies, the commensal E. coli population remained unchanged by the phage treatment maintaining itself at 108 CFU/mL. Conclusions. Our data indicates that bacteriophage cocktails may be implemented to decolonize some intestinal carriers. However, the individual microbiota composition may have an impact on the development of phage resistance. Mechanisms underlying this phenomenon are likely to be various and complex. Further in vivo studies and protein expression experiments are needed to confirm our observations and hypotheses.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Veterinary Bacteriology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > General Bacteriology

UniBE Contributor:

Bernasconi, Odette Joëlle; Campos-Madueno, Edgar Igor; Perreten, Vincent and Endimiani, Andrea

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2213-7165

Publisher:

Elsevier

Funders:

[4] Swiss National Science Foundation

Projects:

[1124] Whole Genome and Plasmid Sequencing for MDR Enterobacteriaceae Simultaneously Isolated from Multiple Human and Non-Human Settings: Deciphering Impact, Risks, and Dynamics for Resistance Transmission and Spread

Language:

English

Submitter:

Andrea Endimiani

Date Deposited:

24 Jun 2020 16:59

Last Modified:

27 Jul 2020 01:33

Publisher DOI:

10.1016/j.jgar.2020.05.018

BORIS DOI:

10.7892/boris.144827

URI:

https://boris.unibe.ch/id/eprint/144827

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