Advanced search
Add to list

The PlySs9 endolysin contains unique catalytic domains and is a potential therapeutic against Streptococcus suis

(2019)
Author
Organization
Abstract
Increasing resistance to antibiotics amongst livestock has forced the discovery of alternative techniques to continue treating bacterial infections successfully. Bacteriophage-encoded peptidoglycan hydrolases, also referred to as endolysins, are able to lyse the bacterial cell wall and offer possible applications in food safety, human health and veterinary science. The treatment of Streptococcus suis infections in pigs specifically involves the latter three. Its zoonotic nature is a potential human health threat and the economic loss of $100 million per year is devastating on the swine industry. Preventing on-farm disease outbreaks is extremely difficult and current approaches to eradicate S. suis from herds are often ineffective. Therefore, a pressing need to identify and evaluate S. suis-specific endolysins arises. A bioinformatic approach was conducted to identify proteins in bacteriophage genomes with similar homology to known endolysin catalytic domains. We chose five candidates for synthesis, expression, purification and characterization upon discovery of lytic activity assayed by turbidity reduction. Binding capacity was evaluated by fluorescent microscopy. PlySs9 represents our lead candidate and is predicted to contain an N-terminal amidase catalytic domain, a central LysM-based cell wall binding domain, and a C-terminal CHAP catalytic domain. We have determined the optimal conditions for the lytic activity of PlySs9, characterized its broad activity spectrum, and investigated its ability to disrupt biofilms. Active-site residues were detected through site-directed mutagenesis. We also assessed the contribution of each individual domain to activity or binding. Lastly, a triple-acting enzyme of PlySs9 was engineered using three unique, potentially synergistic lytic domains to reduce the risk of resistance development. These results indicate that the broad lytic spectrum of PlySs9 and its derivatives have the potential to be used as therapeutic agents against S. suis infections.
Keywords
Antimicrobial Use, Pigs, Protein Structure, Antimicrobial Resistance.

Citation

Please use this url to cite or link to this publication:

MLA
Linden, Sara B., et al. The PlySs9 Endolysin Contains Unique Catalytic Domains and Is a Potential Therapeutic against Streptococcus Suis . 2019.
APA
Linden, S. B., Vander Elst, N., & Nelson, D. C. (2019). The PlySs9 endolysin contains unique catalytic domains and is a potential therapeutic against Streptococcus suis . Presented at the Conference of Research Workers in Animal Diseases, Chicago, Illinois.
Chicago author-date
Linden, Sara B., Niels Vander Elst, and Daniel C. Nelson. 2019. “The PlySs9 Endolysin Contains Unique Catalytic Domains and Is a Potential Therapeutic against Streptococcus Suis .” In .
Chicago author-date (all authors)
Linden, Sara B., Niels Vander Elst, and Daniel C. Nelson. 2019. “The PlySs9 Endolysin Contains Unique Catalytic Domains and Is a Potential Therapeutic against Streptococcus Suis .” In .
Vancouver
1.
Linden SB, Vander Elst N, Nelson DC. The PlySs9 endolysin contains unique catalytic domains and is a potential therapeutic against Streptococcus suis . In 2019.
IEEE
[1]
S. B. Linden, N. Vander Elst, and D. C. Nelson, “The PlySs9 endolysin contains unique catalytic domains and is a potential therapeutic against Streptococcus suis ,” presented at the Conference of Research Workers in Animal Diseases, Chicago, Illinois., 2019.
@inproceedings{8634039,
  abstract     = {Increasing resistance to antibiotics amongst livestock has forced the discovery of alternative techniques to continue treating bacterial infections successfully. Bacteriophage-encoded peptidoglycan hydrolases, also referred to as endolysins, are able to lyse the bacterial cell wall and offer possible applications in food safety, human health and veterinary science. The treatment of Streptococcus suis infections in pigs specifically involves the latter three. Its zoonotic nature is a potential human health threat and the economic loss of $100 million per year is devastating on the swine industry. Preventing on-farm disease outbreaks is extremely difficult and current approaches to eradicate S. suis from herds are often ineffective. Therefore, a pressing need to identify and evaluate S. suis-specific endolysins arises. A bioinformatic approach was conducted to identify proteins in bacteriophage genomes with similar homology to known endolysin catalytic domains. We chose five candidates for synthesis, expression, purification and characterization upon discovery of lytic activity assayed by turbidity reduction. Binding capacity was evaluated by fluorescent microscopy. PlySs9 represents our lead candidate and is predicted to contain an N-terminal amidase catalytic domain, a central LysM-based cell wall binding domain, and a C-terminal CHAP catalytic domain. We have determined the optimal conditions for the lytic activity of PlySs9, characterized its broad activity spectrum, and investigated its ability to disrupt biofilms. Active-site residues were detected through site-directed mutagenesis. We also assessed the contribution of each individual domain to activity or binding. Lastly, a triple-acting enzyme of PlySs9 was engineered using three unique, potentially synergistic lytic domains to reduce the risk of resistance development. These results indicate that the broad lytic spectrum of PlySs9 and its derivatives have the potential to be used as therapeutic agents against S. suis infections.},
  author       = {Linden, Sara B. and Vander Elst, Niels and Nelson, Daniel C.},
  keywords     = {Antimicrobial Use,Pigs,Protein Structure,Antimicrobial Resistance.},
  location     = {Chicago, Illinois.},
  title        = {The PlySs9 endolysin contains unique catalytic domains and is a potential therapeutic against Streptococcus suis },
  year         = {2019},
}