Vol.65 No.5 September 2017
Investigations of invasive streptococcal infection based on next generation sequencing
1)Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, Japan
2)Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University
Abstract
With the advent of the next generation sequencer (NGS), whole genome analysis of pathogenic microorganisms has become very familiar. This review introduces our investigations of an invasive streptococcal infection using an NGS. 1) The isolation frequency of Streptococcus dysgalactiae subsp. equisimilis (SDSE) from invasive streptococcal infection cases has been increasing recently. We reported for the first time on the complete genome sequence of SDSE strains, and found that SDSE is the closest relative of group A streptococcus (GAS), while SDSE lacks several important virulence factors. 2) Although it is known that GAS achieves hypervirulence during the infectious stage in both humans and mice through disrupting covRS, a two-component regulatory system, it is unclear if the other genes are also disrupted in the in vivo environment. We used an in vivo mutagenesis scheme to obtain mutant GAS strains, and identified the location of the generated mutations with an NGS. 3) We generated several GAS mutants, of which various transcriptional regulators were deleted. After mouse infection of the mutants, their transcriptome data were obtained by RNA-seq, genes were clustered, and their network was analyzed. 4) Although there are a number of transcriptional regulators in GAS, there are only a few reports describing the regulons, which are directly regulated by certain transcriptional regulators. The relationships among the regulatory network and the role(s) of transcriptional factors during the pathogenesis of STSS are therefore not well-understood. We utilized ChIP-seq and RNA-seq to explore the genes regulated by CovRS. 5) Our institute is one of the designated medical institutions for specified infectious diseases such as Ebola, Dengue, MERS and Zika fever. We encountered a patient who showed symptoms suspected as being caused by MERS-CoV infection since he had traveled in the UAE and Morocco for sightseeing and had ridden a camel. MERS-CoV, in turn, is actually one of the infectious diseases caused by GAS. We were able to analyze the whole genome sequence of the isolate.
Key word
Streptococcus pyogenes（Group A streptococci）, Streptococcus dysgalactiae subsp. equisimilis
Received
January 16, 2017
Accepted
April 19, 2017
Jpn. J. Chemother. 65 (5): 745-750, 2017
