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A Phage-Like Chromosomal Island Impacts Global Transcription Patterns and Virulence in Streptococcus anginosus

ABSTRACT: Streptococcus anginosus is an important cause of brain and liver abscesses, meningitis, appendicitis, female genital tract infection, neonatal sepsis, and bacteremia. Recent studies show that S. anginosus is responsible for around 30% of streptococci associated purulent infections of internal organs. Genome sequencing of S. anginosus identified a phage-like chromosomal island (SanCI) integrated into the DNA mismatch repair operon. In S. pyogenes, related chromosomal islands (SpyCI) integrated into the same operon confer a mutator phenotype as well as alter global gene regulation, including the increased expression of many virulence factors. We hypothesized that SanCI will also alter global transcription patterns and virulence in S. anginosus. The SanCI from strain F0211 was introduced into a SanCI-free S. anginosus strain (J4211) by natural transformation. To provide a selectable marker for transformation, gene strA, encoding a predicted transcriptional regulator, was replaced in F0211 with the gene conferring erythromycin resistance (ermB), which after transfer created strain OKSan3. A functional copy of strA was then returned to this derivative of J4211, creating strain OKSan4. RNA sequencing (RNA-seq) of strains J4211, OKSan4 and OKSan3 confirmed that the addition of the SanCI altered S. anginosus global transcription patterns with increased expression of virulence, stress response and competence factors in a growth phase dependent manner. Virulence studies using Galleria mellonella as an acute infection model showed significantly increased inflammation and mortality in larvae challenged with strains OKSan4 and OKSan3 as compare to SanCI-free strain J4211. qRT-PCR analysis supported these results, revealing that antimicrobial factors of G. mellonella were more highly expressed after infection with OKSan4 compare to J4211 infection. Further, RNA-seq suggested that SanCI-encoded gene strA may encode one of the factors responsible for altered global transcriptional changes. The result of this study along with our previous studies in S. pyogenes demonstrate that streptococcal chromosomal islands are a unique class of virulence factors that improve the fitness of their host cell by altering global transcription patterns and increasing virulence.

ORGANISM(S): Streptococcus anginosus

PROVIDER: GSE124234 | GEO | 2018/12/21

REPOSITORIES: GEO

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Project description:Streptococcus dysgalactiae subsp. equeisimilis (SDSE) has Lancefield group G or C antigens. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe and US. Although SDSE possesses similar virulence factors to S. pyogenes including streptolysin S (SLS) and streptolysin O (SLO), some important S. pyogenes virulence factors including active superantigens, SpeB and a hyarulonic acids capsule are missing in SDSE genome. The mechanisms and the key virulence factors for causing invasive diseases by SDSE are poorly understood. Here, we analyzed the transcriptome of SDSE in vivo using the murine sepsis model, revealing the strategy of SDSE to destruct host tissues with the virulence factors and to scavenge depleted nutrients. The expression of SLO operon increased at relatively early stage of infection while the SLS and hyaluronidases upregulated after 4h post infection. Microarray data suggested that SDSE degraded host tissue polysaccharides by streptococcal-secreting poly/oligosaccharide lyases and simultaneously used the Entner-Doudoroff pathway to metabolize acquired carbohydrates. A global negative virulence gene regulator CsrRS of SDSE modulated the expressions of genes encoding SLS and the carbohydrate metabolism enzymes. Moreover, csrS deficient mutant induced sever systemic hemolysis in mice. The most frequently isolated stG6792 strains from invasive disease secreted abundant SLS and SLO rather than other SDSE emm types, indicating the relationship between the SLS and SLO productions and poor outcome by the stG6792 strain infection. Our findings suggest that the concomitant regulation of virulence factors destructing the host tissues and metabolic enzymes play an important role to produce invasive diseases by SDSE. To analyze gene expressions in group G streptococci with the murine infection model, we developed a custom microarray for Streptococcus dysgalactiae subsp. equisimilis (SDSE) based on the genome sequences of three SDSE strains; GGS_124, ATCC12923 and RE378. We intraperitoneally inoculated 10^8 CFU of GGS_124 stain and the csrS deficient mutant into ddY mice. Bacterial cells were collected from the abdominal cavity at 0, 2, 4 and 8 h post infection. GGS_124 cells were also collected from OD600=0.6 culture in brain heart infusion broth as a control.

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A Phage-Like Chromosomal Island Impacts Global Transcription Patterns and Virulence in Streptococcus anginosus

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