Genome Mining and Comparative Analysis of Streptococcus intermedius Causing Brain Abscess in a Child

Abstract

Streptococcus intermedius (SI) is associated with prolonged hospitalization and low survival rates. The genetic mechanisms involved in brain abscess development and genome evolution in comparison to other members of the Streptococcus anginosus group are understudied. We performed a whole-genome comparative analysis of an SI isolate, LAU_SINT, associated with brain abscess following sinusitis with all SI genomes in addition to S. constellatus and S. anginosus. Selective pressure on virulence factors, phages, pan-genome evolution and single-nucleotide polymorphism analysis were assessed. The structural details of the type seven secretion system (T7SS) was elucidated and compared with different organisms. ily and nanA were both abundant and conserved. Nisin resistance determinants were found in 47% of the isolates. Pan-genome and SNPs-based analysis didn’t reveal significant geo-patterns. Our results showed that two SC isolates were misidentified as SI. We propose the presence of four T7SS modules (I–IV) located on various genomic islands. We detected a variety of factors linked to metal ions binding on the GIs carrying T7SS. This is the first detailed report characterizing the T7SS and its link to nisin resistance and metal ions binding in SI. These and yet uncharacterized T7SS transmembrane proteins merit further studies and could represent potential therapeutic targets.

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

“…These, however, might not provide enough discriminatory power between closely related species. For instance, 16S rRNA gene-based phylogeny suffered from low resolution (Schouls et al, 2003), and it was not a suitable approach to differentiate S. intermedius from S. constellatus (Issa et al, 2019). On the other hand, cpn60 outperformed both 16S rRNA and rpoB in differentiation between individual strains (Olson et al, 2013).…”

“…The advent of WGS has provided, however, a better resolution and discriminatory power between closely related organisms at the species and strain levels by looking into the accumulation of single-nucleotide polymorphisms (SNPs), core genome conservation, virulence potential, horizontally transferred genetic material, and microevolution within the host (Olson et al, 2013). This approach was better at comparing and identifying the isolates at the species and strain level (Issa et al, 2019). Although 42 genome assemblies of S. intermedius are currently available on the NCBI database (last accessed on 08/05/2019), S. intermedius still remains under-represented compared to other SAG members and other medically relevant streptococci ( Figure 1B).…”

“…Cytokines are also released from human macrophages upon stimulation by histone-like DNA binding proteins (HLPs), and this alters the nucleoid architecture to control gene transcription (Liu et al, 2008). Adhesion to the ECM is also facilitated by the surface protein (psaA), enolase (eno) for plasminogen binding, and pullulanase (pulA) (Issa et al, 2019). The PsaA protein ortholog in S. pneumoniae has been shown to bind to the adhesion molecule E-cadherin (Anderton et al, 2007).…”

“…Bacterial invasion is assisted by a complete Streptococcus Invasion locus (sil) system detected in S. intermedius (Issa et al, 2019). The sil genes improve virulence and delay wound healing in S. pyogenes infections (Salim et al, 2008).…”

“…Very few recent studies were published correlating clinical outcomes, morbidity, and mortality in SAG-infected patients, while the prediction of the disease outcome in S. intermedius-infected patients remains unrealistic. Also, the advent of whole-genome sequencing (WGS) has provided in-depth information into S. intermedius genome organization, virulence, and secretion systems that might help in highlighting specific genetic markers and single point variants in various SAG members, as demonstrated in the work done by Issa et al (2019). Understanding the various genetic components contributing to abscess development could also help in finding novel targets for therapy and vaccine development.…”