The Fällman group has published a new article in Nature Communications with the title: “RNA atlas of human bacterial pathogens uncovers stress dynamics linked to infection”. “I think the results obtained from this study could be very helpful for better understanding of adaptation strategies of different bacterial pathogens.”-says Kemal Avican, the main driver of the study, one of the corresponding authors.
Bacterial pathogens have to cope with stressful environments in human host. Their response with the activity of gene products enables them to adapt to those stressful environments and cause troublesome infections. Therefore, genes involved in the adaptation are potential targets for new antimicrobials.
Researchers of this study has exposed 32 different bacterial human pathogens to 11 stress conditions mimicking human host environments and catalogued their transcriptome. Investigation of over 100 000 genes enabled them to identify stress responsive genes, common and unique regulatory responses, and processes participating in different stress responses. By comparing the gene expressions to publicly available data, they could show that these responses are employed during infection of two clinically important pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. They have shown that a significant proportion of responses is originated from known and putative novel non-coding RNAs, indicating existence of potential novel ncRNAs in the dataset to be discovered. The RNA atlas is deposited on an interactive and user-friendly webpage at www.pathogenex.org.
Picture: Maria Fällman and Kemal Avican at Umeå University campus. Credit: Gabrielle Beans Picón.
“The generation of gene groups from over 100 000 genes and their transcriptional regulation under stress conditions simplified cross-microbial comparisons of gene regulation.”-Kemal comments. “It also allowed comprehensive understanding of gene regulation during infection as have been shown that in vitro measured stress responses could be seen during infections with S. aureus and P. aeruginosa. The universal stress responders (USRs, conserved genes responding to multiple stress conditions) have high potential to provide hints for identification of targets for novel antimicrobials as we could identify some USRs which are already known targets. The quality, depth and size of the data produced in this study provide an excellent resource for developing artificial intelligence (AI) algorithms to solve complex problems related to infection biology. “
Kemal concludes that “Along my journey with this study, I realised that an AI-powered systems biology approach with wide range of bacterial pathogens could help us to decode bacterial adaptation strategies to combat infections. “
Illustration of the PATHOgenex, a freely available online RNA atlas of 32 human bacterial pathogens exposed to 11 infection relevant stress. Illutsration by Kemal Avican.
The principal investigator behind this project is Professor Maria Fällman, who is the other corresponding author.
“The strength of the data collection is the high quality of the data, which in contrast to many other “big data sets” is controlled and validated by being produced in the same way. Kemal has visited the labs of experts for the different pathogens to perform the stress experiments, and he also prepared all libraries for sequencing. There are many research groups that have contributed with specific knowledge for the different pathogens and Kemal, who initiated the project, has done a tremendous job in organizing the work.” – says Maria. Other collaborative efforts that made this work possible, was our collaborations with researchers at FIMM, at University of Helsinki, our Finnish sister node within the Nordic EMBL Partnership for Molecular Medicine, for development and building of the database and associated web interface, and researchers in Basel, who Kemal visited and worked with for developing the formula for PTDEX score´s to enable cross-microbial comparisons. The resulting database (www.pathogenex.org), which has been available via bioRxiv, has already attracted a lot of interest and several research groups have contacted us.”
RNA atlas of human bacterial pathogens uncovers stress dynamics linked to infection
Kemal Avican, Jehad Aldahdooh, Matteo Togninalli, A. K. M. Firoj Mahmud, Jing Tang, Karsten M. Borgwardt, Mikael Rhen & Maria Fällman
Nature Communications volume 12, Article number: 3282 (2021)
The original article is available here:
Text written by Nóra Lehotai, Kemal Avican and Maria Fällman.