Comparative Genomics Reveals Insight Into Streptococcus Anginosus Invasive Disease
Objectives: Although Streptococcus anginosus group bacteria are a normal part of the human oral microflora, they are also associated with a wide range of infections, from dental abscesses to septicemia. The direct mechanisms by which these commensal bacteria become invasive are unclear. One possibility is that poor oral hygiene results in environmental conditions that facilitate invasion regardless of the specific genotype of the commensal strain; another is that certain genotypes are more likely to take advantage of environmental opportunities to become invasive. Methods: Whole genome alignments of sequenced isolates were used to identify synteny groups as well as core genes for phylogenetic analysis. Genome-Wide-Association-Studies (GWAS) was used to identify candidate loci for the invasive index. Polymerase chain reaction (PCR) analysis of strains found in the blood of septic patients confirmed the presence or absence of loci in clinical isolates. Results: 792 core genes and six types of core synteny were identified from 74 sequenced isolates of Streptococcus anginosus. Phylogenetic analysis identified a new distinct cluster of 31 strains, predominantly isolated from healthy urogenital tract. The remaining 43 strains contained eight invasive strains isolated from bacteremic patient blood samples. These invasive strains did not fall into a single phylogenetic cluster, but were biased towards one specific clade. GWAS identified key loci allowing us to develop a PCR-based invasive index, the utility of which was confirmed by screening 37 additional clinical isolates from the blood of septic patients. Conclusions: These data suggest that certain gentoypes of S. anginosus are more likely to become invasive given the opportunity. A PCR-based invasive index can be used to identify such strains.