title: Minimum core genome sequence typing of bacterial pathogens: a unified approach for clinical and public health microbiology.
abstract: Bacterial pathogens impose a heavy health burden worldwide. In the new era of high-throughput sequencing and online bioinformatics, real-time genome typing of infecting agents, and in particular those with potential severe clinical outcomes, holds promise for guiding clinical care to limit the detrimental effects of infections and to prevent potential local or global outbreaks. Here, we sequenced and compared 85 isolates of Streptococcus suis, a zoonotic human and swine pathogen, wherein we analyzed 32 recognized serotypes and 75 sequence types representing the diversity of the species and the human clinical isolates with high public health significance. We found that 1,077 of the 2,469 genes are shared by all isolates. Excluding 201 common but mobile genes, 876 genes were defined as the minimum core genome (MCG) of the species. Of 190,894 single-nucleotide polymorphisms (SNPs) identified, 58,501 were located in the MCG genes and were referred to as MCG SNPs. A population structure analysis of these MCG SNPs classified the 85 isolates into seven MCG groups, of which MCG group 1 includes all isolates from human infections and outbreaks. Our MCG typing system for S. suis provided a clear separation of groups containing human-associated isolates from those containing animal-associated isolates. It also separated the group containing outbreak isolates, including those causing life-threatening streptococcal toxic shock-like syndrome, from sporadic or less severe meningitis or bacteremia-only isolates. The typing system facilitates the application of genome data to the fields of clinical medicine and epidemiology and to the surveillance of S. suis. The MCG groups may also be used as the taxonomical units of S. suis to define bacterial subpopulations with the potential to cause severe clinical infections and large-scale outbreaks.
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Han
authors.initials: H
authors.lastname: Zheng
authors.forename: Ruiting
authors.initials: R
authors.lastname: Lan
authors.forename: Haiyin
authors.initials: H
authors.lastname: Wang
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Du
authors.forename: Xuemei
authors.initials: X
authors.lastname: Bai
authors.forename: Shaobo
authors.initials: S
authors.lastname: Ji
authors.forename: Qiong
authors.initials: Q
authors.lastname: Meng
authors.forename: Dong
authors.initials: D
authors.lastname: Jin
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Huaiqi
authors.initials: H
authors.lastname: Jing
authors.forename: Changyun
authors.initials: C
authors.lastname: Ye
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Marcelo
authors.initials: M
authors.lastname: Gottschalk
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D001431:Bacteriological Techniques / Q000379:methods*; D019295:Computational Biology / Q000379:methods; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017720:Molecular Epidemiology / Q000379:methods*; D058889:Molecular Typing / Q000379:methods*; D013290:Streptococcal Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology / Q000662:veterinary; D017011:Streptococcus suis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D013552:Swine; D013553:Swine Diseases / Q000453:epidemiology / Q000382:microbiology; D015047:Zoonoses / Q000453:epidemiology / Q000382:microbiology