title: Characterization of the Pathogenicity of Streptococcus intermedius TYG1620 Isolated from a Human Brain Abscess Based on the Complete Genome Sequence with Transcriptome Analysis and Transposon Mutagenesis in a Murine Subcutaneous Abscess Model.
abstract: Streptococcus intermedius is known to cause periodontitis and pyogenic infections in the brain and liver. Here we report the complete genome sequence of strain TYG1620 (genome size, 2,006,877 bp; GC content, 37.6%; 2,020 predicted open reading frames [ORFs]) isolated from a brain abscess in an infant. Comparative analysis of S. intermedius genome sequences suggested that TYG1620 carries a notable type VII secretion system (T7SS), two long repeat regions, and 19 ORFs for cell wall-anchored proteins (CWAPs). To elucidate the genes responsible for the pathogenicity of TYG1620, transcriptome analysis was performed in a murine subcutaneous abscess model. The results suggest that the levels of expression of small hypothetical proteins similar to phenol-soluble modulin β1 (PSMβ1), a staphylococcal virulence factor, significantly increased in the abscess model. In addition, an experiment in a murine subcutaneous abscess model with random transposon (Tn) mutant attenuation suggested that Tn mutants with mutations in 212 ORFs in the Tn mutant library were attenuated in the murine abscess model (629 ORFs were disrupted in total); the 212 ORFs are putatively essential for abscess formation. Transcriptome analysis identified 37 ORFs, including paralogs of the T7SS and a putative glucan-binding CWAP in long repeat regions, to be upregulated and attenuated in vivo This study provides a comprehensive characterization of S. intermedius pathogenicity based on the complete genome sequence and a murine subcutaneous abscess model with transcriptome and Tn mutagenesis, leading to the identification of pivotal targets for vaccines or antimicrobial agents for the control of S. intermedius infections.
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.|Department of Biomolecular Science, Toho University, Chiba, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hasegawa
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sekizuka
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sugi
authors.affiliation: Department of Pediatrics, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kawakami
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ogasawara
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kato
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan makokuro@niid.go.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuroda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001922:Brain Abscess / Q000382:microbiology*; D004251:DNA Transposable Elements; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D058977:Molecular Sequence Annotation; D009154:Mutation; D017192:Skin Diseases, Bacterial / Q000382:microbiology* / Q000473:pathology; D034367:Streptococcus intermedius / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D059467:Transcriptome; D014774:Virulence
chemical_list: D004251:DNA Transposable Elements
keywords: Streptococcus; brain abscess; genomics; murine model; transposon mutagenesis; whole-genome sequence