title: The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
abstract: Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by <3-logs. A combination of 0.05 mg PlySs2 + 0.05 mg gentamicin reduced S. suis by >5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans.
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, United States of America.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Gilmer
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, United States of America.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, United States of America.
authors.forename: Mya
authors.initials: M
authors.lastname: Thandar
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, United States of America.
authors.forename: Chad W
authors.initials: CW
authors.lastname: Euler
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York, United States of America.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001435:Bacteriophages; D003001:Cloning, Molecular; D004798:Enzymes / Q000494:pharmacology*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage; D051379:Mice; D009297:Nasal Mucosa / Q000382:microbiology*; D010406:Penicillins / Q000627:therapeutic use; D013290:Streptococcal Infections / Q000188:drug therapy*; D017108:Streptococcus Phages; D017011:Streptococcus suis / Q000472:pathogenicity*; D034421:Sus scrofa; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy*; D015047:Zoonoses / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D004798:Enzymes; D005839:Gentamicins; D010406:Penicillins; C028806:lysin, streptococcus bacteriophage