RNA atlas of human bacterial pathogens uncovers stress dynamics linked to infection

Kemal Avican,Jing Tang,A K M Firoj Mahmud,Matteo Togninalli,Maria Fällman,Karsten M Borgwardt,Mikael Rhen,Jehad Aldahdooh

doi:10.1038/s41467-021-23588-w

Abstract

Bacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials. Here, we report large-scale transcriptomic analyses of 32 human bacterial pathogens grown under 11 stress conditions mimicking human host environments. The potential relevance of the in vitro stress conditions and responses is supported by comparisons with available in vivo transcriptomes of clinically important pathogens. Calculation of a probability score enables comparative cross-microbial analyses of the stress responses, revealing common and unique regulatory responses to different stresses, as well as overlapping processes participating in different stress responses. We identify conserved and species-specific ‘universal stress responders’, that is, genes showing altered expression in multiple stress conditions. Non-coding RNAs are involved in a substantial proportion of the responses. The data are collected in a freely available, interactive online resource (PATHOgenex).

Highlights

Bacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials
Helicobacter pylori are successful in adaptation to acidic environments capable to colonize the stomach, which mostly relies on enzymatic activities of proteins such as urease leading to the formation of ammonia neutralizing gastric acid[7]
To asses quality of read mappings, transcript length coverage was evaluated for each strain using the replicate with the lowest number of total reads

Summary

Introduction

Bacterial processes necessary for adaption to stressful host environments are potential targets for new antimicrobials. One is the comprehensive suite of infectionrelevant conditions described for S. enterica where the transcriptomes are cataloged in a database[18] Another valuable resource for retrieving information of regulatory networks associated with host cell invasion is a collection of differential expression profiles of Salmonella mutated in genes encoding selected transcription factors[19]. The BACTOME database with stationary phase expression profiles of 96 Pseudomonas aeruginosa clinical isolates allows linkages of phenotype, genotype, and transcriptome[21] While these resources provide important information about gene expression and regulation under different conditions in specific bacterial pathogens, there is no resource providing information of diverse bacterial pathogens exposed to similar host-related conditions. We show that non-coding RNAs are differentially regulated in response to stressful environments and that novel ncRNAs can be explored from the dataset

Methods

Results

Conclusion