DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Characterization of a leukocidin identified in Staphylococcus pseudintermedius

Abstract

Bacterial infections from Staphylococcus pseudintermedius are the most common cause of skin infections (pyoderma) affecting dogs. Two component pore-forming leukocidins are a family of potent toxins secreted by staphylococci and consist of S (slow) and F (fast) components. They impair the innate immune system, the first line of defense against these pathogens. Seven different leukocidins have been characterized in Staphylococcus aureus, some of which are host and cell specific. Through genome sequencing and analysis of the S. pseudintermedius secretome using liquid chromatography mass spectrometry we identified two proteins, named “LukS-I” and “LukF-I”, encoded on a degenerate prophage contained in the genome of S. pseudintermedius isolates. Phylogenetic analysis of LukS-I components in comparison to the rest of the leukocidin family showed that LukS-I was most closely related to S. intermedius LukS-I, S. aureus LukE and LukP, whereas LukF-I was most similar to S. intermedius LukF-I S. aureus gamma hemolysin subunit B. The killing effect of recombinant S. pseudintermedius LukS-I and LukF-I on canine polymorphonuclear leukocytes was determined using a flow cytometry cell permeability assay. The cytotoxic effect occurred only when the two recombinant proteins were combined. Engineered mutant versions of the two-component pore-forming leukocidins, produced through amino acids substitutions at selectedmore » points, were not cytotoxic. Anti-Luk-I produced in dogs against attenuated proteins reduced the cytotoxic effect of native canine leukotoxin which highlights the importance of Luk-I as a promising component in a vaccine against canine S. pseudintermedius infections.« less

Authors:
ORCiD logo [1];  [1];  [2];  [1]; ORCiD logo [1]
  1. Univ. of Tennessee, Knoxville, TN (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1495979
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 9; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Abouelkhair, Mohamed A., Bemis, David A., Giannone, Richard J., Frank, Linda A., and Kania, Stephen A. Characterization of a leukocidin identified in Staphylococcus pseudintermedius. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0204450.
Abouelkhair, Mohamed A., Bemis, David A., Giannone, Richard J., Frank, Linda A., & Kania, Stephen A. Characterization of a leukocidin identified in Staphylococcus pseudintermedius. United States. https://doi.org/10.1371/journal.pone.0204450
Abouelkhair, Mohamed A., Bemis, David A., Giannone, Richard J., Frank, Linda A., and Kania, Stephen A. Thu . "Characterization of a leukocidin identified in Staphylococcus pseudintermedius". United States. https://doi.org/10.1371/journal.pone.0204450. https://www.osti.gov/servlets/purl/1495979.
@article{osti_1495979,
title = {Characterization of a leukocidin identified in Staphylococcus pseudintermedius},
author = {Abouelkhair, Mohamed A. and Bemis, David A. and Giannone, Richard J. and Frank, Linda A. and Kania, Stephen A.},
abstractNote = {Bacterial infections from Staphylococcus pseudintermedius are the most common cause of skin infections (pyoderma) affecting dogs. Two component pore-forming leukocidins are a family of potent toxins secreted by staphylococci and consist of S (slow) and F (fast) components. They impair the innate immune system, the first line of defense against these pathogens. Seven different leukocidins have been characterized in Staphylococcus aureus, some of which are host and cell specific. Through genome sequencing and analysis of the S. pseudintermedius secretome using liquid chromatography mass spectrometry we identified two proteins, named “LukS-I” and “LukF-I”, encoded on a degenerate prophage contained in the genome of S. pseudintermedius isolates. Phylogenetic analysis of LukS-I components in comparison to the rest of the leukocidin family showed that LukS-I was most closely related to S. intermedius LukS-I, S. aureus LukE and LukP, whereas LukF-I was most similar to S. intermedius LukF-I S. aureus gamma hemolysin subunit B. The killing effect of recombinant S. pseudintermedius LukS-I and LukF-I on canine polymorphonuclear leukocytes was determined using a flow cytometry cell permeability assay. The cytotoxic effect occurred only when the two recombinant proteins were combined. Engineered mutant versions of the two-component pore-forming leukocidins, produced through amino acids substitutions at selected points, were not cytotoxic. Anti-Luk-I produced in dogs against attenuated proteins reduced the cytotoxic effect of native canine leukotoxin which highlights the importance of Luk-I as a promising component in a vaccine against canine S. pseudintermedius infections.},
doi = {10.1371/journal.pone.0204450},
journal = {PLoS ONE},
number = 9,
volume = 13,
place = {United States},
year = {Thu Sep 27 00:00:00 EDT 2018},
month = {Thu Sep 27 00:00:00 EDT 2018}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Staphylococcus aureus Panton-Valentine Leukocidin Is a Very Potent Cytotoxic Factor for Human Neutrophils
journal, January 2010


Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence
journal, September 2015

  • Yoong, Pauline; Torres, Victor J.
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms9125

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
  • DOI: 10.1093/nar/gkq406

Antimicrobial resistance in methicillin susceptible and methicillin resistant Staphylococcus pseudintermedius of canine origin: Literature review from 1980 to 2013
journal, July 2014


LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis
journal, November 2016

  • Vrieling, Manouk; Boerhout, Eveline M.; van Wigcheren, Glenn F.
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep37759

Inferring Reasons for the Failure of Staphylococcus aureus Vaccines in Clinical Trials
journal, January 2012

  • Bagnoli, Fabio; Bertholet, Sylvie; Grandi, Guido
  • Frontiers in Cellular and Infection Microbiology, Vol. 2
  • DOI: 10.3389/fcimb.2012.00016

Methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius in veterinary medicine
journal, January 2010


Clonal Complexes and Antimicrobial Susceptibility Profiles of Staphylococcus pseudintermedius Isolates from Dogs in the United States
journal, January 2018

  • Videla, Ricardo; Solyman, Samar M.; Brahmbhatt, Akshar
  • Microbial Drug Resistance, Vol. 24, Issue 1
  • DOI: 10.1089/mdr.2016.0250

Structurally Designed Attenuated Subunit Vaccines for S. aureus LukS-PV and LukF-PV Confer Protection in a Mouse Bacteremia Model
journal, June 2013


Dramatic performance of Clostridium thermocellum explained by its wide range of cellulase modalities
journal, February 2016


Fractionation of a leucocidin from Staphylococcus aureus
journal, October 1959


Characterisation of a synergohymenotropic toxin produced by Staphylococcus intermedius
journal, December 1995


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
  • DOI: 10.1038/nprot.2015.053

SignalP 4.0: discriminating signal peptides from transmembrane regions
journal, September 2011

  • Petersen, Thomas Nordahl; Brunak, Søren; von Heijne, Gunnar
  • Nature Methods, Vol. 8, Issue 10
  • DOI: 10.1038/nmeth.1701

SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies
journal, February 2017


Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus
journal, January 2017

  • Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel M. L.
  • Scientific Reports, Vol. 7, Issue 1
  • DOI: 10.1038/srep40660

Staphylococcus aureus LukAB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1
journal, June 2013

  • DuMont, A. L.; Yoong, P.; Day, C. J.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 26
  • DOI: 10.1073/pnas.1305121110

The potential use of toxin antibodies as a strategy for controlling acute Staphylococcus aureus infections
journal, April 2012


Purification of the two components of leucocidin from Staphylococcus aureus
journal, April 1960


Progress Toward a Staphylococcus aureus Vaccine
journal, December 2011

  • Daum, R. S.; Spellberg, B.
  • Clinical Infectious Diseases, Vol. 54, Issue 4
  • DOI: 10.1093/cid/cir828

PHASTER: a better, faster version of the PHAST phage search tool
journal, May 2016

  • Arndt, David; Grant, Jason R.; Marcu, Ana
  • Nucleic Acids Research, Vol. 44, Issue W1
  • DOI: 10.1093/nar/gkw387

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
  • DOI: 10.1093/jac/dkq078

Use of Label-Free Quantitative Proteomics To Distinguish the Secreted Cellulolytic Systems of Caldicellulosiruptor bescii and Caldicellulosiruptor obsidiansis
journal, April 2011

  • Lochner, Adriane; Giannone, Richard J.; Rodriguez, Miguel
  • Applied and Environmental Microbiology, Vol. 77, Issue 12
  • DOI: 10.1128/AEM.02811-10

PHAST: A Fast Phage Search Tool
journal, June 2011

  • Zhou, Y.; Liang, Y.; Lynch, K. H.
  • Nucleic Acids Research, Vol. 39, Issue suppl
  • DOI: 10.1093/nar/gkr485

Heterologous protein production in the yeast Kluyveromyces lactis
journal, May 2006


The effects of Staphylococcus aureus leukotoxins on the host: cell lysis and beyond
journal, February 2013


Heterologous expression of Mytilus californianus foot protein three (Mcfp-3) in Kluyveromyces lactis
journal, January 2008

  • Platko, Joseph D.; Deeg, Matthew; Thompson, Valery
  • Protein Expression and Purification, Vol. 57, Issue 1
  • DOI: 10.1016/j.pep.2007.08.013

Fine-scale population structure and evidence for local adaptation in Australian giant black tiger shrimp (Penaeus monodon) using SNP analysis
journal, September 2020


Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.
text, January 2017

  • Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel ML
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.24528

Multilocus sequence typing for characterization of Staphylococcus pseudintermedius
text, January 2013

  • Eberlein, L. C.; Videla, R.; Wagenaar, J. A.
  • American Society for Microbiology
  • DOI: 10.7892/boris.43831

Identifying Proteomic LC‐MS/MS Data Sets with Bumbershoot and IDPicker
journal, March 2012


Characterisation of a synergohymenotropic toxin produced by Staphylococcus intermedius
journal, December 1995


The effects of Staphylococcus aureus leukotoxins on the host: cell lysis and beyond
journal, February 2013


SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies
journal, February 2017


Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence
journal, September 2015

  • Yoong, Pauline; Torres, Victor J.
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms9125

SignalP 4.0: discriminating signal peptides from transmembrane regions
journal, September 2011

  • Petersen, Thomas Nordahl; Brunak, Søren; von Heijne, Gunnar
  • Nature Methods, Vol. 8, Issue 10
  • DOI: 10.1038/nmeth.1701

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
  • DOI: 10.1038/nprot.2015.053

LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis
journal, November 2016

  • Vrieling, Manouk; Boerhout, Eveline M.; van Wigcheren, Glenn F.
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep37759

Fractionation of a leucocidin from Staphylococcus aureus
journal, October 1959


Staphylococcus aureus LukAB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1
journal, June 2013

  • DuMont, A. L.; Yoong, P.; Day, C. J.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 26
  • DOI: 10.1073/pnas.1305121110

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
  • DOI: 10.1093/jac/dkq078

PHASTER: a better, faster version of the PHAST phage search tool
journal, May 2016

  • Arndt, David; Grant, Jason R.; Marcu, Ana
  • Nucleic Acids Research, Vol. 44, Issue W1
  • DOI: 10.1093/nar/gkw387

Heterologous protein production in the yeast Kluyveromyces lactis
journal, May 2006


Dramatic performance of Clostridium thermocellum explained by its wide range of cellulase modalities
journal, February 2016


Acetamide Selection of Kluyveromyces lactis Cells Transformed with an Integrative Vector Leads to High-Frequency Formation of Multicopy Strains
journal, June 2007

  • Read, J. D.; Colussi, P. A.; Ganatra, M. B.
  • Applied and Environmental Microbiology, Vol. 73, Issue 16
  • DOI: 10.1128/aem.02253-06

Kluyveromyces lactis LAC4 Promoter Variants That Lack Function in Bacteria but Retain Full Function in K. lactis
journal, November 2005


Staphylococcus aureus Elaborates Leukocidin AB To Mediate Escape from within Human Neutrophils
journal, March 2013

  • DuMont, Ashley L.; Yoong, Pauline; Surewaard, Bas G. J.
  • Infection and Immunity, Vol. 81, Issue 5
  • DOI: 10.1128/iai.00095-13

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
  • DOI: 10.1128/jcm.02421-12

Bovine Staphylococcus aureus Secretes the Leukocidin LukMF′ To Kill Migrating Neutrophils through CCR1
journal, June 2015


Structurally Designed Attenuated Subunit Vaccines for S. aureus LukS-PV and LukF-PV Confer Protection in a Mouse Bacteremia Model
journal, June 2013


Staphylococcus aureus Panton-Valentine Leukocidin Is a Very Potent Cytotoxic Factor for Human Neutrophils
journal, January 2010


The potential use of toxin antibodies as a strategy for controlling acute Staphylococcus aureus infections
journal, April 2012


Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.
text, January 2017

  • Koop, Gerrit; Vrieling, Manouk; Storisteanu, Daniel ML
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.24528

Detección de Staphylococcus pseudintermedius resistentes a meticilina y a otros antimicrobianos de uso habitual en la clínica en piodermias caninas
journal, December 2017

  • Giacoboni, Gabriela; Vinocur, Florencia; Fauret, Natali
  • Analecta Veterinaria, Vol. 37, Issue 2
  • DOI: 10.24215/15142590e012

Works referencing / citing this record:

Identification, cloning and characterization of SpEX exotoxin produced by Staphylococcus pseudintermedius
journal, July 2019


Underrated Staphylococcus species and their role in antimicrobial resistance spreading
journal, January 2020

  • Rossi, Ciro César; Pereira, Monalessa Fábia; Giambiagi-deMarval, Marcia
  • Genetics and Molecular Biology, Vol. 43, Issue 1 suppl 2
  • DOI: 10.1590/1678-4685-gmb-2019-0065

Genome Sequences of Six Prophages Isolated from Staphylococcus pseudintermedius Strains Recovered from Human and Animal Clinical Specimens
journal, July 2019

  • Wipf, Juliette R. K.; Deutsch, Douglas R.; Westblade, Lars F.
  • Microbiology Resource Announcements, Vol. 8, Issue 28
  • DOI: 10.1128/mra.00387-19

Identification, cloning and characterization of SpEX exotoxin produced by Staphylococcus pseudintermedius
journal, July 2019