title: Children with invasive Staphylococcus aureus disease exhibit a potently neutralizing antibody response to the cytotoxin LukAB.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases, The Monroe Carell Jr. Children's Hospital at Vanderbilt, and the Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Thomsen
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Dumont
authors.forename: David B A
authors.initials: DB
authors.lastname: James
authors.forename: Pauline
authors.initials: P
authors.lastname: Yoong
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Saville
authors.forename: Nicole
authors.initials: N
authors.lastname: Soper
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002648:Child; D003603:Cytotoxins / Q000276:immunology*; D005260:Female; D006801:Humans; D007956:Leukocidins / Q000276:immunology*; D008297:Male; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D003603:Cytotoxins; D007956:Leukocidins; D037521:Virulence Factors; C586430:leukocidin AB, Staphylococcus aureus