Li Ming, Wang Changjun, Feng Youjun, Pan Xiuzhen, Cheng Gong, Wang Jing, Ge Junchao, Zheng Feng, Cao Min, Dong Yaqing, Liu Di, Wang Jufang, Lin Ying, Du Hongli, Gao George F, Wang Xiaoning, Hu Fuquan, Tang Jiaqi
Department of Microbiology, Third Military Medical University, Chongqing, China.
PLoS One. 2008 May 7;3(5):e2080. doi: 10.1371/journal.pone.0002080.
Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood.
METHODOLOGY/PRINCIPAL FINDINGS: 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant.
CONCLUSIONS/SIGNIFICANCE: These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.
猪链球菌2型(S. suis 2,SS2)已演变成一种高传染性病原体,在中国引发了最近两次大规模的人类SS2疫情,其特征为中毒性休克样综合征。然而,这种新出现病原体的分子发病机制仍知之甚少。
方法/主要发现:89K是一个新预测的致病岛(PAI),对从这两次SS2疫情中分离出的中国流行菌株具有特异性。进一步的生物信息学分析揭示了位于候选89K PAI中的一个独特的双组分信号转导系统(TCSTS),它与唾液链球菌的SalK/SalR调节系统直系同源。敲除salKR消除了SS2在仔猪实验感染中的致死性。将salKR功能互补到同基因突变体ΔsalKR中恢复了其极高的致病性。定殖实验表明,单独给药时,ΔsalKR突变体无法在仔猪的任何易感组织中定殖。杀菌试验表明,该突变体对多形核白细胞(PMN)介导的杀伤的抗性大大降低。表达微阵列分析显示,在ΔsalKR突变体中有26个不同基因的转录谱发生改变,这些基因下调。
结论/意义:这些发现表明,SalK/SalR对于中国高致病性SS2分离株的完全毒力是必需的,从而为这个通过生物信息学预测的PAI的有效性提供了实验证据。