Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae
| Autor: | Shengnan Xiao, Kaifeng Wu, Yibing Yin, Xuemei Zhang, Zhaoche Shu, Jinghui Zhang, Yuqiang Zheng, Weijie Ye |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Phase Variation
Mutant Virulence Microbiology Virulence factor Transcriptome Mice Bacterial Proteins Virology Recombinase Transcriptional regulation Animals Humans Gene Silencing Gene Alleles SpnD39III Phase variation Chemistry FabT Gene Expression Profiling Gene Expression Regulation Bacterial QR1-502 capsular polysaccharide Cell biology Streptococcus pneumoniae Phenotype A549 Cells Mutation Research Article Transcription Factors |
| Zdroj: | mBio mBio, Vol 12, Iss 4 (2021) |
| ISSN: | 2150-7511 |
| Popis: | 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 D39ΔfabT 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 D39ΔfabT 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 PsrA-dependent and PsrA-independent manners. In addition, compared to D39s, the ΔfabT 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 ΔfabT 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 ΔfabT 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. |
| Databáze: | OpenAIRE |
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