[en] Objectives
The aim of this study was to assess the efficacy of lytic bacteriophages onStaphylococcus aureus causing bovine mastitis, by in vitro and in vivo assays using Galleria mellonella and murine mastitis models.
Methods
Between May and December 2016, tenS. 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 theS. aureus isolates in vitro. A larvae survival rate below 50% was observed at four days post inoculation in the groups infected with a methicillin-sensitive S. aureus isolate and treated with these three phages in vivo. An incomplete recovery of the mice mastitis was observed at 48 hours post inoculation in the groups infected and treated with the ISP phage in vivo.
Conclusions
The observations are much more pronounced statistically between the infected-PBS treated and infected-phage treated groups inG. mellonella and murine mastitis model demonstrating an effect of the phages against S. aureus associated with bovine mastitis.
Duprez, Jean-Noël ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Département des maladies infectieuses et parasitaires (DMI)
Fergestad, M.; Norwegian University of Life Sciences > Department of Food Safety and Infection Biology
De Visscher, A.; Ghent University > Department of Reproduction, Obstetrics and Herd Health > M-team & Mastitis and Milk Quality Research Unit
L'Abee-Lund, T.; Norwegian University of Life Sciences > Department of Food Safety and Infection Biology
De Vliegher, S.; Ghent University > Department of Reproduction, Obstetrics and Herd Health > M-team & Mastitis and Milk Quality Research Unit
Wasteson, Y.; Norwegian University of Life Sciences > Department of Food Safety and Infection Biology
Touzain, F.; ANSES > Ploufragan-Plouzané laboratory > Viral Genetics and Bio-security Unit
Blanchard, Y.; ANSES > Ploufragan-Plouzané laboratory > Viral Genetics and Bio-security Unit,
Lavigne, R.; KU Leuven > Department of Biosystems > Laboratory of Gene Technology
Chanishvili, N.; Eliava Institute of Bacteriophages > R&D Department
Cassart, Dominique ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Département de morphologie et pathologie (DMP)
Mainil, Jacques ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Bactériologie et pathologie des maladies bactériennes
Thiry, Damien ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Bactériologie et pathologie des maladies bactériennes
McCarthy, A.J., Lindsay, J.A., Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host–pathogen interactions. BMC Microbiol, 10, 2010, 173, 10.1186/1471-2180-10-173.
David, M.Z., Daum, R.S., Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23 (2010), 616–687, 10.1128/CMR.00081-09.
Mccarthy, A.J., Lindsay, J.A., Loeffler, A., Are all methicillin-resistant Staphylococcus aureus (MRSA) equal in all hosts? Epidemiological and genetic comparison between animal and human MRSA. Vet Dermatol 23 (2012), e53–e54, 10.1111/j.1365-3164.2012.01072.x.
Petinaki, E., Spiliopoulou, I., Methicillin-resistant Staphylococcus aureus colonization and infection risks from companion animals: current perspectives. Vet Med (Auckl) 6 (2015), 373–382, 10.2147/vmrr.s91313.
Arias, C.A., Barbara, E., Murray, M.D., Antibiotic-resistant bugs in the 21st century – a clinical super-challenge. N Engl J Med 360 (2009), 439–443, 10.1056/NEJMp0804651.
Yalcin, C., Stott, A.W., Logue, D.N., Gunn, J., The economic impact of mastitis-control procedures used in Scottish dairy herds with high bulk-tank somatic-cell counts. Prev Vet Med 41 (1999), 135–149.
Halasa, T., Huijps, K., Osterås, O., Hogeveen, H., Economic effects of bovine mastitis and mastitis management: a review. Vet Q 29 (2007), 18–31, 10.1080/01652176.2007.9695224.
McGrath, S., van Sinderen, D., Bacteriophage: genetics and molecular biology. 2007, Caister Academic Press, Cork.
Salmond, G.P.C., Fineran, P.C., A century of the phage: past, present and future. Nat Rev Microbiol 13 (2015), 777–786, 10.1038/nrmicro3564.
Beeton, M.L., Alves, D.R., Enright, M.C., Jenkins, A.T.A., Assessing phage therapy against Pseudomonas aeruginosa using a Galleria mellonella infection model. Int J Antimicrob Agents 46 (2015), 196–200, 10.1016/j.ijantimicag.2015.04.005.
Vandersteegen, K., Kropinski, A.M., Nash, J.H.E., Noben, J.-P., Hermans, K., Lavigne, R., Romulus and Remus, two phage isolates representing a distinct clade within the Twortlikevirus genus, display suitable properties for phage therapy applications. J Virol 87 (2013), 3237–3247, 10.1128/JVI.02763-12.
Vandersteegen, K., Mattheus, W., Ceyssens, P.J., Bilocq, F., de Vos, D., Pirnay, J.P., et al. Microbiological and molecular assessment of bacteriophage ISP for the control of Staphylococcus aureus. PLoS One, 6, 2011, e24418, 10.1371/journal.pone.0024418.
Ajuebor, J., Buttimer, C., Arroyo-Moreno, S., Chanishvili, N., Gabriel, E.M., O'Mahony, J., et al. Comparison of Staphylococcus phage K with close phage relatives commonly employed in phage therapeutics. Antibiotics, 7, 2018, 37, 10.3390/antibiotics7020037.
Sambrook, J., Green, M., 4th ed. Molecular cloning: a laboratory manual, vol. 1, 2012, Cold Spring Harbor Press, New York, 10.3724/SP.J.1141.2012.01075.
Mazzocco, A., Waddell, T.E., Lingohr, E., Johnson, R.P., Enumeration of bacteriophages using the small drop plaque assay system. Kropinski, A.M., (eds.) Bacteriophages methods protocols in public health, 2009, Humana Press, Guelph, Ontario, 81–85, 10.1007/978-1-60327-164-6.
Kutter, E., Phage host range and efficiency of plating. Methods Mol Biol, 2009, 141–149, 10.1007/978-1-60327-164-6.
Breyne, K., Honaker, R.W., Hobbs, Z., Richter, M., Zaczek, M., Spangler, T., et al. Efficacy and safety of a bovine-associated Staphylococcus aureus phage cocktail in a murine model of mastitis. Front Microbiol, 8, 2017, 2348, 10.3389/fmicb.2017.02348.
Koboldt, D.C., Zhang, Q., Larson, D.E., Shen, D., McLellan, M.D., Lin, L., et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 22 (2012), 568–576, 10.1101/gr.129684.111.
Belleghem, J., Van Deschaght, P., Vergauwen, B., Study of Staphylococcus aureus phage ISP and derived proteins potential use as antibacterial therapeutics and anti-inflammatory properties. 2012, University of Ghent, Ghent.
Manohar, P., Tamhankar, A.J., Lundborg, C.S., Escherichia coliTherapeutic characterization and efficacy of bacteriophage cocktails infecting, Klebsiella pneumoniae, and Enterobacter species. Front Microbiol 10 (2019), 1–12, 10.3389/fmicb.2019.00574.
Costa, P., Pereira, C., Gomes, A.T.P.C., Almeida, A., Escherichia coliEfficiency of single phage suspensions and phage cocktail in the inactivation of and Salmonella typhimurium: an in vitro preliminary study 2019. Microorganisms, 7, 2019, 94, 10.3390/microorganisms7040094.
Dabrowska, K., Abedon, S.T., Pharmacologically aware phage therapy: pharmacodynamic and pharmacokinetic obstacles to phage antibacterial action in animal and human bodies. Microbiol Mol Biol Rev 83 (2019), e00012–e19, 10.1128/MMBR.00012-19.
Azam, A.H., Tanji, Y., Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy. Appl Microbiol Biotechnol 103 (2019), 2121–2131, 10.1007/s00253-019-09629-x.
Manohar, P., Nachimuthu, R., Lopes, B.S., The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model. BMC Microbiol 18 (2018), 1–11, 10.1186/s12866-018-1234-4.
Jeon, J., Park, J.H., Yong, D., Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia. BMC Microbiol 19 (2019), 1–14, 10.1186/s12866-019-1443-5.
Thiry, D., Passet, V., Danis-wlodarczyk, K., Lood, C., Wagemans, J., De Sordi, L., et al. New bacteriophages against emerging lineages ST23 and ST258 of Klebsiella pneumoniae and efficacy assessment in Galleria mellonella larvae. Viruses, 11, 2019, 411, 10.3390/v11050411.
Angelichio, M.J., Camilli, A., Minireview: in vivo expression technology. Infect Immun 70 (2002), 6518–6523, 10.1128/IAI.70.12.6518.
Gogoi-tiwari, J., Williams, V., Waryah, C.B., Costantino, P., Al-salami, H., Mathavan, S., et al. Mammary gland pathology subsequent to acute infection with strong versus weak biofilm forming Staphylococcus aureus bovine mastitis isolates: a pilot study using non-invasive mouse mastitis model. PLoS One 12 (2017), 1–19, 10.1371/journal.pone.0170668.
Iwano, H., Inoue, Y., Takasago, T., Kobayashi, H., Furusawa, T., Taniguchi, K., et al. Bacteriophage (SA012 has a broad host range against Staphylococcus aureus and effective lytic capacity in a mouse mastitis model. Biology (Basel), 7, 2018, 8, 10.3390/biology7010008.
Wang, Z., Zheng, P., Ji, W., Fu, Q., Wang, H., Yan, Y., et al. SLPW: a virulent bacteriophage targeting methicillin-resistant Staphylococcus aureus in vitro and in vivo. Front Microbiol 7 (2016), 1–10, 10.3389/fmicb.2016.00934.
Van Belleghem, J.D., Dąbrowska, K., Vaneechoutte, M., Barr, J.J., Bollyky, P.L., Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses, 2019, 11, 10.3390/v11010010.
Kay, B.D., Fildes, P., The inactivation of a bacteriophage by a component of papain. Biochem J 75 (1960), 139–145.
Ly-Chatain, M.H., The factors affecting effectiveness of treatment in phages therapy. Front Microbiol, 5, 2014, 51, 10.3389/fmicb.2014.00051.
