title: Evolutionary inactivation of a sialidase in group B Streptococcus.
abstract: Group B Streptococcus (GBS) is a leading cause of bacterial sepsis and meningitis in newborns. GBS possesses a protein with homology to the pneumococcal virulence factor, NanA, which has neuraminidase (sialidase) activity and promotes blood-brain barrier penetration. However, phylogenetic sequence and enzymatic analyses indicate the GBS NanA ortholog has lost sialidase function - and for this distinction we designate the gene and encoded protein nonA/NonA. Here we analyze NonA function in GBS pathogenesis, and through heterologous expression of active pneumococcal NanA in GBS, potential costs of maintaining sialidase function. GBS wild-type and ΔnonA strains lack sialidase activity, but forced expression of pneumococcal NanA in GBS induced degradation of the terminal sialic acid on its exopolysaccharide capsule. Deletion of nonA did not change GBS-whole blood survival or brain microvascular cell invasion. However, forced expression of pneumococcal NanA in GBS removed terminal sialic acid residues from the bacterial capsule, restricting bacterial proliferation in human blood and in vivo upon mouse infection. GBS expressing pneumococcal NanA had increased invasion of human brain microvascular endothelial cells. Thus, we hypothesize that nonA lost enzyme activity allowing the preservation of an effective survival factor, the sialylated exopolysaccharide capsule.
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.|Department of Pediatrics School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.|Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Hirose
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Department of Pediatrics School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: Department of Pediatrics School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sumitomo
authors.affiliation: Department of Molecular Microbiology and Ob/Gyn, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Lewis
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
authors.affiliation: Department of Pediatrics School of Medicine, University of California San Diego, La Jolla, CA, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.|Rady Children's Hospital, San Diego, CA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000382:microbiology; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D006801:Humans; D051379:Mice; D050296:Microbial Viability; D009439:Neuraminidase / Q000235:genetics*; D010802:Phylogeny; D013290:Streptococcal Infections / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000201:enzymology* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D009439:Neuraminidase