Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity
Abstract
Staphylococcus pseudintermedius is a major opportunistic bacterial pathogen and the leading cause of pyoderma in dogs. In canines it is also often associated with infections of the urinary system and wounds and occasionally infects people. Widespread antimicrobial resistance has made the development of alternative treatments a high priority. The development of a staphylococcal vaccine, however, has proven challenging. Identification of virulence factors that inhibit phagocytosis and avoid innate immunity may play a significant role in preventing or treating infection with S. pseudintermedius. In this study, we identified a putative 5'-nucleotidase provisionally named SpAdsA, a S. pseudintermedius cell- wall protein encoded by SpAdsA. SpAdsA shares approximately 52% identity with the orthologous protein of Staphylococcus aureus and 14.8% identity with that of Streptococcus suis type2. It catalyzes the dephosphorylation of adenosine triphosphate and attenuation of this enzyme with critical amino acid substitutions nearly eliminated its hydrolytic activity. Furthermore, exogenous adenosine inhibited phagocytosis of S. pseudintermedius by canine neutrophils and monocytes. Conversely, the addition of SpAdsA inhibitor or A2A adenosine receptor antagonist impaired the capacity of S. pseudintermedius to escape from killing by phagocytic cells. The neutralizing ability of canine antibody produced against SpAdsA-M was determined. Taken together, these results suggest that SpAdsAmore »
- Authors:
-
[3];
- Univ. of Tennessee, Knoxville, TN (United States); Univ. of Sadat City, Menoufia (Egypt)
- Univ. of Tennessee, Knoxville, TN (United States)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1661202
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Veterinary Microbiology
- Additional Journal Information:
- Journal Volume: 246; Journal Issue: 1; Journal ID: ISSN 0378-1135
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 5'-nucleotidase; Staphylococcus pseudintermedius; SpAdsA; PMNs; Immune evasion; Virulence; Vaccine
Citation Formats
Abouelkhair, Mohamed A., Frank, Linda A., Bemis, David A., Giannone, Richard J., and Kania, Stephen A. Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity. United States: N. p., 2020.
Web. doi:10.1016/j.vetmic.2020.108720.
Abouelkhair, Mohamed A., Frank, Linda A., Bemis, David A., Giannone, Richard J., & Kania, Stephen A. Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity. United States. https://doi.org/10.1016/j.vetmic.2020.108720
Abouelkhair, Mohamed A., Frank, Linda A., Bemis, David A., Giannone, Richard J., and Kania, Stephen A. Sat .
"Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity". United States. https://doi.org/10.1016/j.vetmic.2020.108720. https://www.osti.gov/servlets/purl/1661202.
@article{osti_1661202,
title = {Staphylococcus pseudintermedius 5'-nucleotidase suppresses canine phagocytic activity},
author = {Abouelkhair, Mohamed A. and Frank, Linda A. and Bemis, David A. and Giannone, Richard J. and Kania, Stephen A.},
abstractNote = {Staphylococcus pseudintermedius is a major opportunistic bacterial pathogen and the leading cause of pyoderma in dogs. In canines it is also often associated with infections of the urinary system and wounds and occasionally infects people. Widespread antimicrobial resistance has made the development of alternative treatments a high priority. The development of a staphylococcal vaccine, however, has proven challenging. Identification of virulence factors that inhibit phagocytosis and avoid innate immunity may play a significant role in preventing or treating infection with S. pseudintermedius. In this study, we identified a putative 5'-nucleotidase provisionally named SpAdsA, a S. pseudintermedius cell- wall protein encoded by SpAdsA. SpAdsA shares approximately 52% identity with the orthologous protein of Staphylococcus aureus and 14.8% identity with that of Streptococcus suis type2. It catalyzes the dephosphorylation of adenosine triphosphate and attenuation of this enzyme with critical amino acid substitutions nearly eliminated its hydrolytic activity. Furthermore, exogenous adenosine inhibited phagocytosis of S. pseudintermedius by canine neutrophils and monocytes. Conversely, the addition of SpAdsA inhibitor or A2A adenosine receptor antagonist impaired the capacity of S. pseudintermedius to escape from killing by phagocytic cells. The neutralizing ability of canine antibody produced against SpAdsA-M was determined. Taken together, these results suggest that SpAdsA likely plays an important role in S. pseudintermedius virulence and that attenuated SpAdsA may be a good candidate for inclusion in a vaccine against S. pseudintermedius.},
doi = {10.1016/j.vetmic.2020.108720},
journal = {Veterinary Microbiology},
number = 1,
volume = 246,
place = {United States},
year = {Sat May 16 00:00:00 EDT 2020},
month = {Sat May 16 00:00:00 EDT 2020}
}
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Works referenced in this record:
Complete Genome Sequence of Staphylococcus pseudintermedius Type Strain LMG 22219
journal, February 2017
- Abouelkhair, Mohamed A.; Riley, Matthew C.; Bemis, David A.
- Genome Announcements, Vol. 5, Issue 7
Characterization of a leukocidin identified in Staphylococcus pseudintermedius
journal, September 2018
- Abouelkhair, Mohamed A.; Bemis, David A.; Giannone, Richard J.
- PLOS ONE, Vol. 13, Issue 9
Characterization of recombinant wild-type and nontoxigenic protein A from Staphylococcus pseudintermedius
journal, July 2018
- Abouelkhair, Mohamed A.; Bemis, David A.; Kania, Stephen A.
- Virulence, Vol. 9, Issue 1
Complete Genome Sequences of Three Staphylococcus pseudintermedius Strains Isolated from Botswana
journal, March 2018
- Abouelkhair, Mohamed A.; Thompson, Riley; Riley, Matthew C.
- Genome Announcements, Vol. 6, Issue 10
Identification, cloning and characterization of SpEX exotoxin produced by Staphylococcus pseudintermedius
journal, July 2019
- Abouelkhair, Mohamed A.; Bemis, David A.; Giannone, Richard J.
- PLOS ONE, Vol. 14, Issue 7
Expression and function of protein A in Staphylococcus pseudintermedius
journal, March 2018
- Balachandran, Manasi; Bemis, David A.; Kania, Stephen A.
- Virulence, Vol. 9, Issue 1
Regulation of Neutrophil Function by Adenosine
journal, April 2012
- Barletta, Kathryn E.; Ley, Klaus; Mehrad, Borna
- Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 32, Issue 4
Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation
journal, November 2006
- Bours, M. J. L.; Swennen, E. L. R.; Di Virgilio, F.
- Pharmacology & Therapeutics, Vol. 112, Issue 2
Broad and Effective Protection against Staphylococcus aureus Is Elicited by a Multivalent Vaccine Formulated with Novel Antigens
journal, September 2019
- Deng, Jian; Wang, Xiaolei; Zhang, Bao-Zhong
- mSphere, Vol. 4, Issue 5
Purinergic mechanism in the immune system: A signal of danger for dendritic cells
journal, July 2005
- Di Virgilio, Francesco
- Purinergic Signalling, Vol. 1, Issue 3
Mechanisms of ATP Release by Inflammatory Cells
journal, April 2018
- Dosch, Michel; Gerber, Joël; Jebbawi, Fadi
- International Journal of Molecular Sciences, Vol. 19, Issue 4
Extracellular Nucleotide Catabolism by the Group B Streptococcus Ectonucleotidase NudP Increases Bacterial Survival in Blood
journal, February 2014
- Firon, Arnaud; Dinis, Marcia; Raynal, Bertrand
- Journal of Biological Chemistry, Vol. 289, Issue 9
The Staphylococcus intermedius group of bacterial pathogens: species re-classification, pathogenesis and the emergence of meticillin resistance: Recent studies of the Staphylococcus intermedius group
journal, October 2009
- Ross Fitzgerald, J.
- Veterinary Dermatology, Vol. 20, Issue 5-6
Immune evasion by staphylococci
journal, December 2005
- Foster, Timothy J.
- Nature Reviews Microbiology, Vol. 3, Issue 12
Status of vaccine research and development of vaccines for Staphylococcus aureus
journal, June 2016
- Giersing, Birgitte K.; Dastgheyb, Sana S.; Modjarrad, Kayvon
- Vaccine, Vol. 34, Issue 26
A 2A receptors in inflammation and injury: lessons learned from transgenic animals
journal, December 2007
- Haskó, György; Pacher, Pál
- Journal of Leukocyte Biology, Vol. 83, Issue 3
Geneious Basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data
journal, April 2012
- Kearse, M.; Moir, R.; Wilson, A.
- Bioinformatics, Vol. 28, Issue 12
The Phyre2 web portal for protein modeling, prediction and analysis
journal, May 2015
- Kelley, Lawrence A.; Mezulis, Stefans; Yates, Christopher M.
- Nature Protocols, Vol. 10, Issue 6
Streptococcus suis Adenosine Synthase Functions as an Effector in Evasion of PMN-mediated Innate Immunity
journal, January 2014
- Liu, Peng; Pian, Yaya; Li, Xueqin
- The Journal of Infectious Diseases, Vol. 210, Issue 1
Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms
journal, December 2019
- Miller, Lloyd S.; Fowler, Vance G.; Shukla, Sanjay K.
- FEMS Microbiology Reviews, Vol. 44, Issue 1
The effects of intravenous infusions of selective adenosine A1-receptor and A2-receptor agonists on myocardial reperfusion injury
journal, February 1992
- Norton, Elizabeth D.; Jackson, Edwin K.; Turner, Michael B.
- American Heart Journal, Vol. 123, Issue 2
Clonal spread of methicillin-resistant Staphylococcus pseudintermedius in Europe and North America: an international multicentre study
journal, March 2010
- Perreten, V.; Kadlec, K.; Schwarz, S.
- Journal of Antimicrobial Chemotherapy, Vol. 65, Issue 6
Neutrophils in innate host defense against Staphylococcus aureus infections
journal, November 2011
- Rigby, Kevin M.; DeLeo, Frank R.
- Seminars in Immunopathology, Vol. 34, Issue 2
Complete Genome Sequences of Three Important Methicillin-Resistant Clinical Isolates of Staphylococcus pseudintermedius
journal, October 2016
- Riley, Matthew C.; Perreten, Vincent; Bemis, David A.
- Genome Announcements, Vol. 4, Issue 5
Adenosine A2-Receptor Activation at Reperfusion Reduces Infarct Size and Improves Myocardial Wall Function in Dog Heart
journal, January 1993
- Schlack, Wolfgang; Schäfer, Markus; Uebing, Anselm
- Journal of Cardiovascular Pharmacology, Vol. 22, Issue 1
Purinergic receptors and nucleotide processing ectoenzymes: Their roles in regulating mesenchymal stem cell functions
journal, January 2014
- Scarfì, Sonia
- World Journal of Stem Cells, Vol. 6, Issue 2
Multilocus Sequence Typing for Characterization of Staphylococcus pseudintermedius
journal, October 2012
- Solyman, S. M.; Black, C. C.; Duim, B.
- Journal of Clinical Microbiology, Vol. 51, Issue 1
Staphylococcus aureus synthesizes adenosine to escape host immune responses
journal, September 2009
- Thammavongsa, Vilasack; Kern, Justin W.; Missiakas, Dominique M.
- Journal of Experimental Medicine, Vol. 206, Issue 11
Enzymatic properties of Staphylococcus aureus adenosine synthase (AdsA)
journal, January 2011
- Thammavongsa, Vilasack; Schneewind, Olaf; Missiakas, Dominique M.
- BMC Biochemistry, Vol. 12, Issue 1
The critical role of adenosine A2A receptors in downregulation of inflammation and immunity in the pathogenesis of infectious diseases
journal, May 2003
- Thiel, Manfred; Caldwell, Charles C.; Sitkovsky, Michail V.
- Microbes and Infection, Vol. 5, Issue 6
3DLigandSite: predicting ligand-binding sites using similar structures
journal, May 2010
- Wass, Mark N.; Kelley, Lawrence A.; Sternberg, Michael J. E.
- Nucleic Acids Research, Vol. 38, Issue suppl_2
Methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius in veterinary medicine
journal, January 2010
- Weese, J. Scott; van Duijkeren, Engeline
- Veterinary Microbiology, Vol. 140, Issue 3-4
PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes
journal, May 2010
- Yu, Nancy Y.; Wagner, James R.; Laird, Matthew R.
- Bioinformatics, Vol. 26, Issue 13
Streptococcal 5′-Nucleotidase A (S5nA), a Novel Streptococcus pyogenes Virulence Factor That Facilitates Immune Evasion
journal, December 2015
- Zheng, Lisa; Khemlani, Adrina; Lorenz, Natalie
- Journal of Biological Chemistry, Vol. 290, Issue 52