title: A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method.
abstract: The increasing emergence of multi-drug resistant streptococci poses a serious threat to public health worldwide. Bacteriophage lysins are promising alternatives to antibiotics; however, their narrow lytic spectrum restricted to closely related species is a central shortcoming to their translational development. Here, we describe an efficient method for rapid screening of engineered chimeric lysins and report a unique "chimeolysin", ClyR, with robust activity and an extended-spectrum streptococcal host range against most streptococcal species, including S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis, as well as representative enterococcal and staphylococcal species (including MRSA and VISA). ClyR is the first lysin that demonstrates activity against the dominant dental caries-causing pathogen as well as the first lysin that kills all four of the bovine mastitis-causing pathogens. This study demonstrates the success of the screening method resulting in a powerful lysin with potential for treating most streptococcal associated infections.
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Linden
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.|Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Nelson
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D001433:Bacteriolysis / Q000187:drug effects*; D002417:Cattle; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004926:Escherichia coli; D005260:Female; D058507:Host Specificity / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D008892:Milk / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology*; D013290:Streptococcal Infections; D013291:Streptococcus / Q000187:drug effects / Q000502:physiology*
chemical_list: D011994:Recombinant Proteins