The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.

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...

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Main Authors: Daniel B Gilmer, Jonathan E Schmitz, Mya Thandar, Chad W Euler, Vincent A Fischetti
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5207509?pdf=render
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spelling doaj-584db489c53d44668c9e774fe48e82ea2020-11-25T02:27:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e016918010.1371/journal.pone.0169180The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.Daniel B GilmerJonathan E SchmitzMya ThandarChad W EulerVincent A FischettiStreptococcus 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.http://europepmc.org/articles/PMC5207509?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Daniel B Gilmer
Jonathan E Schmitz
Mya Thandar
Chad W Euler
Vincent A Fischetti
spellingShingle Daniel B Gilmer
Jonathan E Schmitz
Mya Thandar
Chad W Euler
Vincent A Fischetti
The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
PLoS ONE
author_facet Daniel B Gilmer
Jonathan E Schmitz
Mya Thandar
Chad W Euler
Vincent A Fischetti
author_sort Daniel B Gilmer
title The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
title_short The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
title_full The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
title_fullStr The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
title_full_unstemmed The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa.
title_sort phage lysin plyss2 decolonizes streptococcus suis from murine intranasal mucosa.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2017-01-01
description 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.
url http://europepmc.org/articles/PMC5207509?pdf=render
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