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 wallanchored 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 ␤1 (PSM␤1), 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. KEYWORDS brain abscess, genomics, murine model, Streptococcus, transposon mutagenesis, whole-genome sequence S treptococcus intermedius, an intraoral commensal bacterium belonging to the Streptococcus anginosus group, is known to cause periodontitis and pyogenic infections in the brain and liver (1-3). Patients with invasive S. intermedius infections have significantly longer hospital stays and higher mortality rates than patients with other S. anginosus group infections (4), suggesting that species identification might be of importance for prognostication.

Characterization of Fusobacterium varium Fv113-g1 isolated from a patient with ulcerative colitis based on complete genome sequence and transcriptome analysis

“…Argus optical mapping with NcoI of Fv113-g1 genome DNA was performed using the Argus system (OpGen, MD, USA) according to the manufacturer’s protocol and previous report by Hasegawa et al . [ 20 ]. Error correction of tentative complete circular sequences was performed using iCORN2 in PAGIT version 1.64 [ 21 ] with Illumina short reads.…”

From Normal Flora to Brain Abscesses: A Review of Streptococcus intermedius

“…Few studies have been performed on the whole-genome molecular characterization and comparative genome analysis of S. intermedius (Olson et al, 2013;Planet et al, 2013;Hasegawa et al, 2017;Issa et al, 2019). A genome announcement for the BA1 strain isolated from an intracranial abscess in a child was published by Planet et al (2013).…”

Simultaneous profiling and cultivation of the skin microbiome of healthy young adult skin for the development of therapeutic agents

“…Possesses antimicrobial activity against food-borne pathogens [20] Propionibacterium acidipropionici Probiotic microorganism modifies number of anaerobes and coliform caecal content [21,22] Propionibacterium avidum Cause of soft tissue infections, potential immunomodulator, treatment of neoplastic and infectious diseases, potential source of active metabolites [23,24,25] Propionibacterium granulosum Immunomodulatory potential [26] Propionibacterium propionicum Cause infections of the lacrimal apparatus [27] Truepera sp. Radiation resistant species, possessing thermostable amylosucrase activity [28,29] Staphylococcus caprae Pathogen, causes bacteraemia and native bone infection [30] Staphylococcus lentus Pathogen, causes peritonitis [31] Streptococcus agalactiae Human pathogen that colonises the urogenital and/or the lower gastro-intestinal tract [32] Streptococcus intermedius Pathogen which causes periodontitis and pyogenic infections in the brain and liver [33] Paracoccus sp. Probiotic dietary supplement for livestock [34] Figure 4.…”