Year: 2011
Type: conference-abstract
Abstract: Background During syphilis infection, the envelope ofTreponema pallidumis constantly exposed to the host environment and, therefore, the most likely target of the host defences against the invading spirochaete. The mechanisms that maintainT pallidumenvelope integrity and functionality, particularly in response to host-induced stresses, are however poorly understood, and their elucidation would likely help identify important pathogenesis-associated molecules, perhaps related toT pallidum'sability to persist in the host despite a robust immune response. We hypothesised that inT pallidum, similarly to other Gram-negative pathogens, the transcription factor σ24 (σ24, encoded by the rpoE gene, TP0092) might be a key element in maintainingT pallidumenvelope homeostasis. Putative σ24 binding motifs can be identified in silico upstream of severalT pallidumgenes that were experimentally shown to be involved in envelope stress response (ESR) inEscherichia coli. Furthermore, during early experimental syphilis σ24 is highly transcribed compared to other σ factors, and its expression increases even more as primary infection progresses. We therefore decided to investigate the possible role of σ24 inT pallidumESR by identifying the components of theT pallidumσ24 regulon. Methods T pallidumcells grown in rabbits were fixed after harvest to crosslink DNA-binding proteins to their target sequences in the chromosome. DNA sequences recognised by σ24 in vivo were isolated using chromatin immunoprecipitation in combination with high-throughput DNA sequencing (ChIP-seq) to identify bound DNA regions. Results Thirty-nine DNA fragments targeted by σ24 were identified in theT pallidumchromosome. Seven of these target genes (lon-1, greA, ftsZ, prfB, htrA, and rpoE) were previously reported to be induced in response to envelope stress inE coli, suggesting that theT pallidumσ24 regulon is likely to be similar to that of other bacteria. Other putative target genes encode transporters, cell division proteins and a subset of motility and chemotaxis proteins. Conclusions InT pallidum, σ24 seems to control genes involved in a variety of cellular processes, including maintenance of envelope homeostasis and barrier function. Additional putative σ24-dependent functions, apparently not directly involved in ESR, could as well be important in helpingT pallidumadapt to the host environment during the infection.
Source: Sexually Transmitted Infections
Institution: University of Washington
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2323429279