In vitro and in vivo assessment of phage therapy against Staphylococcus aureus causing bovine mastitis

C Ngassam-Tchamba; J N Duprez; M Fergestad; A De Visscher; T L'Abee-Lund; S De Vliegher; Y Wasteson; F Touzain; Y Blanchard; R Lavigne; N Chanishvili; D Cassart; J Mainil; D Thiry

doi:10.1016/j.jgar.2020.06.020

In vitro and in vivo assessment of phage therapy against Staphylococcus aureus causing bovine mastitis

J Glob Antimicrob Resist. 2020 Sep:22:762-770. doi: 10.1016/j.jgar.2020.06.020. Epub 2020 Jul 6.

Authors

C Ngassam-Tchamba¹, J N Duprez¹, M Fergestad², A De Visscher³, T L'Abee-Lund², S De Vliegher³, Y Wasteson², F Touzain⁴, Y Blanchard⁴, R Lavigne⁵, N Chanishvili⁶, D Cassart⁷, J Mainil¹, D Thiry⁸

Affiliations

¹ Bacteriology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine and Institute for Fundamental and Applied Research in Animals and Health (FARAH), University of Liège, Quartier Vallée 2, Avenue Cureghem 6, B-4000 Liège, Belgium.
² Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003, 1432 Ås, Norway.
³ M-team & Mastitis and Milk Quality Research Unit, Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
⁴ Viral Genetics and Bio-security Unit, ANSES, Ploufragan-Plouzané laboratory, Rue des Fusillés, 22 440 Ploufragan, France.
⁵ Laboratory of Gene Technology, Department of Biosystems, KU Leuven, 3001 Heverlee, Belgium.
⁶ R & D Department, Eliava Institute of Bacteriophages, 3 Levan Gotua St, T'bilisi, Georgia.
⁷ Department of Morphology and Pathology, Faculty of Veterinary Medicine and Institute for Fundamental and Applied Research in Animals and Health (FARAH), University of Liège, Quartier Vallée 2, Avenue Cureghem 6, B-4000 Liège, Belgium.
⁸ Bacteriology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine and Institute for Fundamental and Applied Research in Animals and Health (FARAH), University of Liège, Quartier Vallée 2, Avenue Cureghem 6, B-4000 Liège, Belgium. Electronic address: damien.thiry@uliege.be.

PMID: 32645442
DOI: 10.1016/j.jgar.2020.06.020

Abstract

Objective: The aim of this study was to assess the efficacy of lytic bacteriophages on Staphylococcus aureus causing bovine mastitis, by in vitro and in vivo assays using Galleria mellonella and murine mastitis models.

Methods: Between May and December 2016, ten S. aureus (five methicillin-resistant and five methicillin-sensitive) isolates were isolated from milk samples of cattle with mastitis in Belgium and Norway. The isolates were assessed in vitro for their susceptibility to four lytic bacteriophages (Romulus, Remus, ISP and DSM105264) and subsequently in vivo in G. mellonella larvae and in murine mastitis model.

Results: Romulus, Remus and ISP showed a lytic activity against the S. aureus isolates in vitro. A larvae survival rate below 50% was observed at 4 days post-inoculation (DPI) in the groups infected with a methicillin-sensitive S. aureus isolate and treated with these three phages in vivo. An incomplete recovery of the mouse mastitis was observed at 48h post-inoculation (HPI) in the groups infected and treated with the ISP phage in vivo_. CONCLUSIONS: The observations are much more pronounced statistically between the infected- phosphate buffered saline (PBS)-treated and infected-phage-treated groups in G. mellonella and the murine mastitis model demonstrating an effect of the phages against S. aureus associated with bovine mastitis.

Keywords: Bovine mastitis; Phage therapy; Staphylococcus aureus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Belgium
Cattle
Female
Humans
Mastitis, Bovine* / therapy
Mice
Phage Therapy*
Staphylococcal Infections* / therapy
Staphylococcal Infections* / veterinary
Staphylococcus aureus