caa a22 4500 605499519 CHVBK 20210128100551.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00253-015-6579-0 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6579-0 Synergistic streptococcal phage λSA2 and B30 endolysins kill streptococci in cow milk and in a mouse model of mastitis [Elektronische Daten] [Mathias Schmelcher, Anne Powell, Mary Camp, Calvin Pohl, David Donovan] Bovine mastitis results in billion dollar losses annually in the USA alone. Streptococci are among the most relevant causative agents of this disease. Conventional antibiotic therapy is often unsuccessful and contributes to development of antibiotic resistance. Bacteriophage endolysins represent a new class of antimicrobials against these bacteria. In this work, we characterized the endolysins (lysins) of the streptococcal phages λSA2 and B30 and evaluated their potential as anti-mastitis agents. When tested in vitro against live streptococci, both enzymes exhibited near-optimum lytic activities at ionic strengths, pH, and Ca2+ concentrations consistent with cow milk. When tested in combination in a checkerboard assay, the lysins were found to exhibit strong synergy. The λSA2 lysin displayed high activity in milk against Streptococcus dysgalactiae (reduction of CFU/ml by 3.5 log units at 100μg/ml), Streptococcus agalactiae (2 log), and Streptococcus uberis (4 log), whereas the B30 lysin was less effective. In a mouse model of bovine mastitis, both enzymes significantly reduced intramammary concentrations of all three streptococcal species (except for B30 vs. S. dysgalactiae), and the effects on mammary gland wet weights and TNFα concentrations were consistent with these findings. Unexpectedly, the synergistic effect determined for the two enzymes in vitro was not observed in the mouse model. Overall, our results illustrate the potential of endolysins for treatment of Streptococcus-induced bovine mastitis. Springer-Verlag Berlin Heidelberg, 2015 Peptidoglycan hydrolase nationallicence Endolysin nationallicence Bacteriophage nationallicence Antimicrobial nationallicence Mastitis nationallicence Streptococcus nationallicence Schmelcher Mathias Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut Powell Anne Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut Camp Mary Statistics Group, Office of the North East Area Director, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut Pohl Calvin Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut Donovan David Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8475-8486 0175-7598 99:20<8475 2015 99 253 https://doi.org/10.1007/s00253-015-6579-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6579-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schmelcher Mathias Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut NATIONALLICENCE 700 1- Powell Anne Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut NATIONALLICENCE 700 1- Camp Mary Statistics Group, Office of the North East Area Director, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut NATIONALLICENCE 700 1- Pohl Calvin Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut NATIONALLICENCE 700 1- Donovan David Animal Biosciences and Biotechnology Laboratory, North East Area, Agricultural Research Service, U.S. Department of Agriculture, 10300 Baltimore Ave, 20705, Beltsville, MD, USA aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8475-8486 0175-7598 99:20<8475 2015 99 253