Genomic analysis and immune response in a murine mastitis model of vB_EcoM-UFV13, a potential biocontrol agent for use in dairy cows

• Published in: Scientific reports Vol. 8; no. 1; pp. 6845 - 12
• Main Authors: da Silva Duarte, Vinícius, Dias, Roberto Sousa, Kropinski, Andrew M., Campanaro, Stefano, Treu, Laura, Siqueira, Carolina, Vieira, Marcella Silva, da Silva Paes, Isabela, Santana, Gabriele Rocha, Martins, Franciele, Crispim, Josicelli Souza, da Silva Xavier, André, Ferro, Camila Geovana, Vidigal, Pedro M. P., da Silva, Cynthia Canêdo, de Paula, Sérgio Oliveira
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 631/326/325; 631/326/432; 64; 64/60; 82; 82/29; 82/51; 82/58; 96/21; Animals; Antibiotics; Antimicrobial resistance; Bacteriophage T4 - genetics; Biological control; Cattle; Dairy cattle; Dairy farms; Disease Models, Animal; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - virology; Female; Genetic structure; Genome, Viral; Genomes; Genomic analysis; Humanities and Social Sciences; Immune response; Immune system; Inflammation; Interleukin 6; Interleukin-6 - immunology; Mastitis; Mastitis, Bovine - immunology; Mastitis, Bovine - microbiology; Mastitis, Bovine - therapy; Mice; Mice, Inbred BALB C; multidisciplinary; Phages; Phylogeny; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α; Virions
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-24896-w

Bovine mastitis remains the main cause of economic losses for dairy farmers. Mammary pathogenic
Escherichia coli
(MPEC) is related to an acute mastitis and its treatment is still based on the use of antibiotics. In the era of antimicrobial resistance (AMR), bacterial viruses (bacteriophages) present as an efficient treatment or prophylactic option. However, this makes it essential that its genetic structure, stability and interaction with the host immune system be thoroughly characterized. The present study analyzed a novel, broad host-range anti-mastitis agent, the
T4virus
vB_EcoM-UFV13 in genomic terms, and its activity against a MPEC strain in an experimental
E. coli
-induced mastitis mouse model. 4,975 Single Nucleotide Polymorphisms (SNPs) were assigned between vB_EcoM-UFV13 and
E. coli
phage T4 genomes with high impact on coding sequences (CDS) (37.60%) for virion proteins. Phylogenetic trees and genome analysis supported a recent infection mix between vB_EcoM-UFV13 and Shigella phage Shfl2. After a viral stability evaluation (e.g pH and temperature), intramammary administration (MOI 10) resulted in a 10-fold reduction in bacterial load. Furthermore, pro-inflammatory cytokines, such as IL-6 and TNF-α, were observed after viral treatment. This work brings the whole characterization and immune response to vB_EcoM-UFV13, a biocontrol candidate for bovine mastitis.