Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae

作者全名："Zhang, Jinghui; Ye, Weijie; Wu, Kaifeng; Xiao, Shengnan; Zheng, Yuqiang; Shu, Zhaoche; Yin, Yibing; Zhang, Xuemei"

作者地址："[Zhang, Jinghui; Wu, Kaifeng; Yin, Yibing; Zhang, Xuemei] Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med Designated, Minist Educ, Chongqing, Peoples R China; [Ye, Weijie] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha, Peoples R China; [Wu, Kaifeng] Zunyi Med Univ, Peoples Hosp Zunyi 1, Affiliated Hosp 3, Dept Lab Med, Zunyi, Guizhou, Peoples R China; [Xiao, Shengnan; Zheng, Yuqiang] Chongqing Med Univ, Childrens Hosp, Dept Med Lab, Chongqing, Peoples R China; [Shu, Zhaoche] Chongqing Med Univ, Affiliated Hosp 1, Dept Blood Transfus, Chongqing, Peoples R China"

通信作者："Zhang, XM (corresponding author), Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med Designated, Minist Educ, Chongqing, Peoples R China."

来源：MBIO

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000693443100004

JCR分区：Q1

影响因子：6.4

年份：2021

卷号：12

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Streptococcus pneumoniae; capsular polysaccharide; phase variation; FabT; SpnD39III

摘要："Streptococcus pneumoniae is an opportunistic pathogen that can alter its cell surface phenotype in response to the host environment. We demonstrated that the transcriptional regulator FabT is an indirect regulator of capsular polysaccharide, an important virulence factor of Streptococcus pneumoniae. Transcriptome analysis between the wild-type D39s and D39DfabT mutant strains unexpectedly identified a differentially expressed gene encoding a site-specific recombinase, PsrA. PsrA catalyzes the inversion of 3 homologous hsdS genes in a type I restriction-modification (RM) system SpnD39III locus and is responsible for the reversible switch of phase variation. Our study demonstrated that upregulation of PsrA in a D39DfabT mutant correlated with an increased ratio of transparent (T) phase variants. Inactivation of the invertase PsrA led to uniform opaque (O) variants. Direct quantification of allelic variants of hsdS derivatives and inversions of inverted repeats indicated that the recombinase PsrA fully catalyzes the inversion mediated by IR1 and IR3, and FabT mediated the recombination of the hsdS alleles in PsrAdependent and PsrA-independent manners. In addition, compared to D39s, the DfabT mutant exhibited reduced nasopharyngeal colonization and was more resistant to phagocytosis and less adhesive to epithelial cells. These results indicated that phase variation in the DfabT mutant also affects other cell surface components involved in host interactions. IMPORTANCE Streptococcus pneumoniae is a major human pathogen, and its virulence factors and especially the capsular polysaccharide have been extensively studied. In addition to virulence components that are present on its cell surface that directly interact with the host, S. pneumoniae undergoes a spontaneous and reversible phase variation that allows survival in different host environments. This phase variation is manipulated by the recombination of allelic hsdS genes that encode the sequence recognition proteins of the type I RM system SpnD39III locus. The recombination of hsdS alleles is catalyzed by the DNA invertase PsrA. Interestingly, we found the opaque colony morphology can be reversed by inactivation of the transcriptional regulator FabT, which regulates fatty acid biosynthesis. Inactivation of FabT leads to a significant decrease in capsule production and systematic virulence, but these phase variations do not correlate with the capsule production. This phase variation is mediated via the upregulated invertase PsrA in the DfabT mutant. These results identify an unexpected link between the specific phase variations and FabT that strongly suggests an underlying mechanism regulating the DNA invertase PsrA."

基金机构："Projects of the National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772153, 81871698]; Chongqing graduate scientific research innovation project [CYB19163]"

基金资助正文："This work was supported by Projects of the National Natural Science Foundation of China (81772153 and 81871698), and J.Z. was supported by a Chongqing graduate scientific research innovation project (CYB19163)."