Children with Invasive Staphylococcus aureus Disease Exhibit a Potently Neutralizing Antibody Response to the Cytotoxin LukAB

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Published inInfection and Immunity Vol. 82; no. 3; pp. 1234 - 1242
Main Authors Thomsen, Isaac P, Dumont, Ashley L, James, David B A, Yoong, Pauline, Saville, Benjamin R, Soper, Nicole, Torres, Victor J, Creech, C Buddy
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.03.2014
Subjects
Antibodies, Neutralizing - immunology
Bacterial Infections
Bacterial Proteins - immunology
Child
Cytotoxins - immunology
Female
Humans
Leukocidins - immunology
Male
Staphylococcal Infections - immunology
Staphylococcus aureus
Staphylococcus aureus - immunology
Virulence Factors - immunology
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Abstract Classifications Services IAI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue IAI About IAI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy Connect to IAI IAI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0019-9567 Online ISSN: 1098-5522 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to IAI .asm.org, visit: IAI       
AbstractList Despite the importance of Staphylococcus aureus as a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined, particularly in children. The purpose of this study was to assess the humoral response to extracellular staphylococcal virulence factors, including the bicomponent leukotoxins, which are critical for the cytotoxicity of S. aureus toward human neutrophils. Children with culture-proven S. aureus infection were prospectively enrolled and stratified by disease type. Fifty-three children were enrolled in the study, of which 90% had invasive disease. Serum samples were obtained during the acute (within 48 h) and convalescent (4 to 6 weeks postinfection) phases, at which point both IgG titers against S. aureus exotoxins were determined, and the functionality of the generated antibodies was evaluated. Molecular characterization of clinical isolates was also performed. We observed a marked rise in antibody titer from acute-phase to convalescent-phase sera for LukAB, the most recently described S. aureus bicomponent leukotoxin. LukAB production by the isolates was strongly correlated with cytotoxicity in vitro, and sera containing anti-LukAB antibodies potently neutralized cytotoxicity. Antibodies to S. aureus antigens were detectable in healthy pediatric controls but at much lower titers than in sera from infected subjects. The discovery of a high-titer, neutralizing antibody response to LukAB during invasive infections suggests that this toxin is produced in vivo and that it elicits a functional humoral response.
Despite the importance of Staphylococcus aureus as a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined, particularly in children. The purpose of this study was to assess the humoral response to extracellular staphylococcal virulence factors, including the bicomponent leukotoxins, which are critical for the cytotoxicity of S. aureus toward human neutrophils. Children with culture-proven S. aureus infection were prospectively enrolled and stratified by disease type. Fifty-three children were enrolled in the study, of which 90% had invasive disease. Serum samples were obtained during the acute (within 48 h) and convalescent (4 to 6 weeks postinfection) phases, at which point both IgG titers against S. aureus exotoxins were determined, and the functionality of the generated antibodies was evaluated. Molecular characterization of clinical isolates was also performed. We observed a marked rise in antibody titer from acute-phase to convalescent-phase sera for LukAB, the most recently described S. aureus bicomponent leukotoxin. LukAB production by the isolates was strongly correlated with cytotoxicity in vitro , and sera containing anti-LukAB antibodies potently neutralized cytotoxicity. Antibodies to S. aureus antigens were detectable in healthy pediatric controls but at much lower titers than in sera from infected subjects. The discovery of a high-titer, neutralizing antibody response to LukAB during invasive infections suggests that this toxin is produced in vivo and that it elicits a functional humoral response.
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Author Victor J. Torres
Nicole Soper
Ashley L. DuMont
C. Buddy Creech
Isaac P. Thomsen
David B. A James
Pauline Yoong
Benjamin R. Saville
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Despite the importance of Staphylococcus aureus as a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined,...
Despite the importance of Staphylococcus aureus as a common invasive bacterial pathogen, the humoral response to infection remains inadequately defined,...
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SubjectTerms Antibodies, Neutralizing - immunology
Bacterial Infections
Bacterial Proteins - immunology
Child
Cytotoxins - immunology
Female
Humans
Leukocidins - immunology
Male
Staphylococcal Infections - immunology
Staphylococcus aureus
Staphylococcus aureus - immunology
Virulence Factors - immunology
Title Children with Invasive Staphylococcus aureus Disease Exhibit a Potently Neutralizing Antibody Response to the Cytotoxin LukAB
URI http://iai.asm.org/content/82/3/1234.abstract
https://www.ncbi.nlm.nih.gov/pubmed/24379282
https://search.proquest.com/docview/1505335938
https://pubmed.ncbi.nlm.nih.gov/PMC3957992
Volume 82
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