title: Streptococcus pneumoniae invades erythrocytes and utilizes them to evade human innate immunity.
abstract: Streptococcus pneumoniae, a Gram-positive bacterium, is a major cause of invasive infection-related diseases such as pneumonia and sepsis. In blood, erythrocytes are considered to be an important factor for bacterial growth, as they contain abundant nutrients. However, the relationship between S. pneumoniae and erythrocytes remains unclear. We analyzed interactions between S. pneumoniae and erythrocytes, and found that iron ion present in human erythrocytes supported the growth of Staphylococcus aureus, another major Gram-positive sepsis pathogen, while it partially inhibited pneumococcal growth by generating free radicals. S. pneumoniae cells incubated with human erythrocytes or blood were subjected to scanning electron and confocal fluorescence microscopic analyses, which showed that the bacterial cells adhered to and invaded human erythrocytes. In addition, S. pneumoniae cells were found associated with human erythrocytes in cultures of blood from patients with an invasive pneumococcal infection. Erythrocyte invasion assays indicated that LPXTG motif-containing pneumococcal proteins, erythrocyte lipid rafts, and erythrocyte actin remodeling are all involved in the invasion mechanism. In a neutrophil killing assay, the viability of S. pneumoniae co-incubated with erythrocytes was higher than that without erythrocytes. Also, H2O2 killing of S. pneumoniae was nearly completely ineffective in the presence of erythrocytes. These results indicate that even when S. pneumoniae organisms are partially killed by iron ion-induced free radicals, they can still invade erythrocytes. Furthermore, in the presence of erythrocytes, S. pneumoniae can more effectively evade antibiotics, neutrophil phagocytosis, and H2O2 killing.
authors.affiliation: Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan ; Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan ; Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mori-Yamaguchi
authors.forename: Hisanori
authors.initials: H
authors.lastname: Domon
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Sakaue
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yagi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nishino
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D004912:Erythrocytes / Q000382:microbiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D057131:Immune Evasion / Q000276:immunology*; D007501:Iron / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000503:physiopathology*; D013211:Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D006861:Hydrogen Peroxide; D007501:Iron