Project description:Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity, which allows the population to adapt to different host environments. Generally, transparent variants are adapted for nasopharyngeal colonization whereas opaque variants are associated with invasive disease. In recent work, colony phase variation was shown to occur by means of recombination events to generate multiple alleles of the hsdS targeting domain of a DNA methylase complex, which mediates epigenetic changes in gene expression. A panel of isogenic strains were created in the well-studied S. pneumoniae TIGR4 background that are “locked” in the transparent (n=4) or opaque (n=2) colony phenotype. The strains had significant differences in colony size which were stable over multiple passages in vitro and in vivo. While there were no significant differences in adherence for the phase-locked mutant strains to immortalized epithelial cells, biofilm formation and viability was reduced for opaque variants in static assays. Nasopharyngeal colonization was stable for all strains, but the mortality rate differed between them. Transcript profiling by RNA-seq analyses revealed that expression of certain virulence factors were increased in a phase-specific manner. As epigenetic regulation of phase variation (often referred to as phasevarion) is emerging as a common theme for mucosal pathogens, these studies serve as a model for future studies of host-pathogen interactions.
Project description:Transcriptomic analysis of Streptococcus pneumoniae TIGR4 wildtype and it's isogenic ccpA mutant, grown in chemically defined media supplemented with physiological levels of carbohydrates to mimic the human nasopharynx and bloodstream. The goal is to examine how anatomical site-specific carbohydrate availability impacts S. pneumoniae physiology and virulence.
Project description:This SuperSeries is composed of the following subset Series: GSE31815: ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + Glucose at MID-log growth phase GSE31816: ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + GLucose at transition-phase of growth (TS) GSE31817: ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + Galactose at MID-log growth phase GSE31818: ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + galactose at transition-phase of growth (TS) Refer to individual Series
Project description:Invasive pneumococcal disease is preceded by asymptomatic colonization of the human nasopharynx by Streptococcus pneumoniae. Progression from colonization to invasion is a watershed in the host-pathogen interaction, and exposes the pneumococcus to markedly different microenvironments. This in turn, requires alterations in gene expression profile to adapt to the new niche. One apparent adaptive mechanism is reversible phase variation between “transparent” and “opaque” colony opacity phenotypes. Transparent phase variants colonize the nasopharynx more efficiently than opaque variants of the same strain, while opaque variants exhibit higher systemic virulence. Previous studies have reported quantitative differences in surface components such as the capsule, teichoic acid and certain surface proteins between the two phenotypes, but the underlying regulatory mechanism is not understood. In the present study, we found no differences in expression of key surface proteins between opaque and transparent variants of S. pneumoniae strain D39, but opaque cells produced five-fold more capsular polysaccharide. Subsequent microarray and real-time RT-PCR analysis showed no differences in capsule gene expression, but several genes involved in uridine monophosphate (UMP) biosynthesis were up-regulated in the opaque phenotype. This correlated with significant increases in the intracellular concentrations of both UMP and UDP-glucose, which are essential precursors for capsule biosynthesis. Our data suggest a novel mechanism for pneumococcal capsule regulation, in which rate-limiting precursor pathways are modulated rather than the capsule biosynthetic genes themselves. Keywords: Phase variants
Project description:Transcriptome comparison of the Streptococcus pneumoniae D39 wild-type grown in CDM Plus 0mM Zn2+ to grown in CDM plus 0.2 mM Zn2+.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain 947.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain 4559.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain 4496.
