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RNA Atlas of Bacterial Human Pathogens Uncovers Stress Dynamics Linked to Bacterial Infections

ABSTRACT: Pathogenic bacteria encounter a variety of stressful host environments during infection. Their responses to meet these challenges protect them from deadly damages and aid in adaption to harmful environments. Bacterial products critical for this protection are therefore interesting as suitable targets for new antimicrobials. To shed light on the complex array of molecular pathways involved in bacterial stress responses we challenged 32 diverse human pathogenic bacteria to 11 infection related stress conditions and catalogued their transcriptomes. Initial analyses of the comprehensive data set showed that beside coding RNAs, known and yet unknown putative novel ncRNAs comprise a significant part of the responses. We also computed a scores for all genes to be used for predictions for their probability to be regulated at certain stresses. The core scores enabled identification of universal stress responders representing conserved gene products involved in basic mechanisms important for responses to multiple stresses. Further, the environmental specific core scores made it possible to predict functions of yet non-characterized and also hypothetical gene products. All data are collected in the PATHOGENEX interactive RNA atlas, which is made available to the research community providing ample opportunities for discovering new aspects of regulatory networks in pathogenic bacteria as well as identification of novel players critical for bacterial infectivity and maintenance of infections.

ORGANISM(S): Francisella tularensis Streptococcus suis Acinetobacter baumannii Streptococcus pneumoniae Neisseria meningitidis Streptococcus agalactiae Achromobacter xylosoxidans Staphylococcus epidermidis Pseudomonas aeruginosa Legionella pneumophila Shigella flexneri Staphylococcus aureus subsp. aureus MRSA252 Haemophilus influenzae Burkholderia pseudomallei Escherichia coli Vibrio cholerae Klebsiella pneumoniae Enterococcus faecalis Salmonella enterica Neisseria gonorrhoeae Staphylococcus aureus subsp. aureus MSSA476 Campylobacter jejuni Helicobacter pylori Mycobacterium tuberculosis Aggregatibacter actinomycetemcomitans Listeria monocytogenes Streptococcus pyogenes Borreliella burgdorferi Yersinia pseudotuberculosis

PROVIDER: GSE152295 | GEO | 2021/04/23

REPOSITORIES: GEO

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Project description:The ability to respond to stress is at the core of an organismâs survival. The hormones epinephrine and norepinephrine play a central role in stress responses in mammals, which require the synchronized interaction of the whole neuroendocrine system. Bacteria also sense and respond to epinephrine and norepinephrine as a means to gauge the metabolic and immune state of the host. Mammalian adrenergic receptors are G-coupled protein receptors (GPCRs), bacteria, however, sense these hormones through histidine sensor kinases (HKs). HKs autophosphorylate in response to multiple signals and transfer this phosphate to response regulators (RRs). Two bacterial adrenergic receptors have been identified in EHEC, QseC and QseE, with QseE being downstream of QseC in this signaling cascade. We mapped the QseC signaling cascade in the deadly pathogen enterohemorrhagic E. coli (EHEC), which exploits this signaling system to promote disease. Through QseC, EHEC activates expression of metabolic, virulence and stress response genes, synchronizing the cell response to these stress hormones. Coordination of these responses is achieved by QseC phosphorylating three of the thirty two EHEC RRs. The QseB RR, which is QseCâs cognate RR, activates the flagella regulon which controls bacteria motility and chemotaxis. The QseF RR, which is phosphorylated by the QseE adrenergic sensor, coordinates expression of virulence genes involved in formation of lesions in the intestinal epithelia by EHEC, and the bacterial SOS stress response. The third RR, KdpE, controls potassium uptake, osmolarity response, and also the formation of lesions in the intestine. Adrenergic regulation of bacterial gene expression shares several parallels with mammalian adrenergic signaling having profound effects in the whole organism. Understanding adrenergic regulation of a bacterial cell is a powerful approach to study the underlying mechanisms of stress and cellular survival. Experiment Overall Design: Microarray comparisons reveal some trends with respect to signaling cascades. Comparative methods were used to identify networks.

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RNA Atlas of Bacterial Human Pathogens Uncovers Stress Dynamics Linked to Bacterial Infections

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