@article{AlbrechtSharmaDittrichetal.2011,
  author    = {Albrecht, Marco and Sharma, Cynthia M. and Dittrich, Marcus T. and M{\"u}ller, Tobias and Reinhardt, Richard and Vogel, J{\"o}rg and Rudel, Thomas},
  title     = {The Transcriptional Landscape of Chlamydia pneumoniae},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69116},
  year      = {2011},
  abstract  = {Background: Gene function analysis of the obligate intracellular bacterium Chlamydia pneumoniae is hampered by the facts that this organism is inaccessible to genetic manipulations and not cultivable outside the host. The genomes of several strains have been sequenced; however, very little information is available on the gene structure and transcriptome of C. pneumoniae. Results: Using a differential RNA-sequencing approach with specific enrichment of primary transcripts, we defined the transcriptome of purified elementary bodies and reticulate bodies of C. pneumoniae strain CWL-029; 565 transcriptional start sites of annotated genes and novel transcripts were mapped. Analysis of adjacent genes for cotranscription revealed 246 polycistronic transcripts. In total, a distinct transcription start site or an affiliation to an operon could be assigned to 862 out of 1,074 annotated protein coding genes. Semi-quantitative analysis of mapped cDNA reads revealed significant differences for 288 genes in the RNA levels of genes isolated from elementary bodies and reticulate bodies. We have identified and in part confirmed 75 novel putative non-coding RNAs. The detailed map of transcription start sites at single nucleotide resolution allowed for the first time a comprehensive and saturating analysis of promoter consensus sequences in Chlamydia. Conclusions: The precise transcriptional landscape as a complement to the genome sequence will provide new insights into the organization, control and function of genes. Novel non-coding RNAs and identified common promoter motifs will help to understand gene regulation of this important human pathogen.},
  subject      = {Chlamydia pneumoniae},
  language  = {en}
}
@phdthesis{Maeurer2006,
  author    = {M{\"a}urer, Andr{\´e} Germar Paul},
  title     = {Analysis of the Chlamydophila pneumoniae and host transcriptome in the acute and iron depletion-mediated persistent infection},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-21415},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {The obligate intracellular gram-negative bacterium, Chlamydophila pneumoniae (Cpn), has a significant impact as an acute and chronic disease-causing pathogen. Its potential to undergo persistent infections has been linked to chronic diseases. Several in vitro cell culture models are used to study persistent conditions, mainly IFN_ stimulation, treatment with antibiotics and iron depletion. Little is known about changes in the Cpn transcriptome during the acute and persistent infection. Therefore, the Cpn transcriptome during its acute developmental cycle and iron depletion-mediated persistence was examined in this study. Based on expression profiles, genes with similar expression changes formed 12 clusters using the self-organizing map algorithm. While other studies define genes based on their onset of transcription, here the important feature for clustering was the expression profile. This turned out to be more appropriate for comparing the time specific relevance of a certain cluster of genes to their proposed functions in the cycle. The Cpn clusters were grouped into the 'Early', 'Mid' and 'Late' classes as described for Ctr. Additionally, a new gene expression class containing genes with steadily increasing expression at the end of the developmental cycle was defined and termed 'Tardy' class. Comparison of the Cpn clusters to published proteomics data showed that genes encoding elementary body (EB) proteins peaked in the 'Late' gene cluster. This indicated that genes of the 'Late' and 'Tardy' class have different roles in RB to EB re-differentiation. Moreover, using lexical comparison the EB mRNA profile was significantly linked to the 'Tardy' cluster class. This provided evidence that initial translation in the cycle might be directed from stable transcripts present in the infectious EB form. Based on these criteria the novel 'Tardy' class was separated from the 'Late' class. The gene ontologies were used to identify specific pathways and physiological functions active during the different phases of development. Additionally, the transcriptome of Cpn in the persistent stage was compared to that of the acute developmental cycle. The Cpn transcriptome was altered in the iron-depletion mediated persistence. Genes upregulated were linked to clusters at the beginning of the developmental cycle, and genes down-regulated were linked to clusters at the end of the developmental cycle. These data provided strong evidence that the Cpn transcriptome during persistence is a gene expression arrest in mid-development. In early acute infection convergently or divergently oriented gene pairs preferentially had an antagonistic expression profile, whereas tandemly oriented gene pairs showed a correlated expression profile. This suggests that the Cpn genome is organized mainly in tandemly arranged operons and in convergently or divergently oriented genes with favored antagonistic profiles. The microarray studies done with the Cpn strain CWL029 also showed expression signals for several genes annotated only for the Cpn strains AR39 and J138. BLAST comparison verified that these genes are also coded in the CWL029 genome. Several of these genes were convergently arranged with their neighboring gene and shared overlapping genome information. Among these were parB, involved in DNA segregation and rpsD, an alternative sigma factor responsible for the transcription at late stages of the developmental cycle. Both genes have been described to have major roles in the chlamydial cycle. These genes had an antagonistic expression profile at the beginning of the acute developmental cycle and in persistence, as described before to be predominant for convergently oriented genes. Real time RT-PCR analysis showed that full-length rpsD mRNA transcripts were down-regulated, whereas short-length rpsD mRNA transcripts were up-regulated during the persistent infection. This demonstrated that the rpsD promoter is activated during the persistent infection and that because of the collision of the RNA polymerases full length transcripts were down-regulated. This sigma factor-independent mechanism is known as 'Transcriptional Interference'. This is the first description on how the alternative sigma factor rpsD might be down-regulated during persistent infections. Finally, the host cell transcriptome was analyzed in the acute and persistent infection mediated by the depletion of iron. Cpn infection triggered the upregulation of relB, involved in an alternative NF-KB signaling pathway. Several genes coding for cell cycle proteins were triggered, including cyclin G2 and cyclin D1 and inhibitors of CDK4. Taken together, this work provides insights into the modulation of the pathogen and the host transcriptome during the acute infection and the iron mediated persistent infection.},
  subject      = {Chlamydia pneumoniae},
  language  = {en}
}