title: Separately or combined, LukG/LukH is functionally unique compared to other staphylococcal bicomponent leukotoxins.
abstract: Staphylococcus aureus is a major human pathogen that elaborates several exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include γ-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin components are classified as either F or S proteins, which are secreted individually and assemble on cell surfaces to form hetero-oligomeric pores resulting in lysis of PMNs and/or erythrocytes. F and S proteins of γ-hemolysin, PVL and LukDE have ∼ 70% sequence homology within the same class and several heterologous combinations of F and S members from these three bicomponent toxin groups are functional. Recently, an additional BCL pair, LukGH (also called LukAB) that has only 30% homology to γ-hemolysin, PVL and LukDE, has been characterized from S. aureus. Our results showed that LukGH was more cytotoxic to human PMNs than PVL. However, LukGH-induced calcium ion influx in PMNs was markedly attenuated and slower than that induced by PVL and other staphylococcal BCLs. In contrast to other heterologous BCL combinations, LukG in combination with heterologous S components, and LukH in combination with heterologous F components did not induce calcium ion entry or cell lysis in human PMNs or rabbit erythrocytes. Like PVL, LukGH induced IL-8 production by PMNs. While individual components LukG and LukH had no cytolytic or calcium influx activity, they each induced high levels of IL-8 transcription and secretion. IL-8 production induced by LukG or LukH was dependent on NF-κB. Therefore, our results indicate LukGH differs functionally from other staphylococcal BCLs.
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America ; Emergency and Critical Care, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Machi
authors.initials: M
authors.lastname: Yanai
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rocha
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Anthony Z
authors.initials: AZ
authors.lastname: Matolek
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Archana
authors.initials: A
authors.lastname: Chintalacharuvu
authors.affiliation: Emergency and Critical Care, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Taira
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Koteswara
authors.initials: K
authors.lastname: Chintalacharuvu
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America ; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: David O
authors.initials: DO
authors.lastname: Beenhouwer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005098:Exotoxins / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007956:Leukocidins / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D016209:Interleukin-8; D007956:Leukocidins; C115217:LukE protein, Staphylococcus aureus; D016328:NF-kappa B; C078284:Panton-Valentine leukocidin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D037521:Virulence Factors; C586430:leukocidin AB, Staphylococcus aureus; C074300:LukF protein, Staphylococcus aureus; D002118:Calcium