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The bacterial lifestyle that disguises stressful adaptations

ABSTRACT: The stringent stress response, mediated by the signalling molecule guanosine penta(tetra)-phosphate (p)ppGpp, has recently gained more attraction as a potential new therapeutic target. However, interference of a global mediator could lead to unwanted side effects, therefore warrants detailed mechanistic understanding. We used RNA-Seq to investigate the transcriptional landscape of a Pseudomonas aeruginosa ppGpp-deficient strain under non-stressful conditions. In exponential growth phase in nutrient-rich broth, the lack of ppGpp led to >1600 transcriptional changes, which provided a novel aspect of the importance of ppGpp in general rather than having the traditional stress/starvation induced changes. Intracellular protein tracking indicated that RelA was bound to the ribosome while SpoT localized at the cell poles. Commonly dysregulated functional systems were divided into 34 clusters and revealed individual genes that might belong to the same pathway as other known adjacent regulon members. The regulatory network of ppGpp included global transcriptional regulators AlgR, OxyR, LasR, and AmrZ that further indirectly linked the stress response to secretion systems and polysaccharide production. The stress response directly influenced the expression of quorum sensing and other downstream effectors including AMB toxin production, the ECF-sigma factor PvdS, the transcriptional regulator PtxS, the two-component response regulator PprB, and various proteases such as ImpA, PA0572, ClpP2, and AprA.

ORGANISM(S): Pseudomonas aeruginosa PAO1

PROVIDER: GSE147132 | GEO | 2020/08/12

REPOSITORIES: GEO

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Project description:Oxidative stress caused by exposure to reactive oxygen species (ROS), is a major challenge for aerobic and especially anaerobic organisms. Bacteria coordinate the response to oxidative stress through the LysR-type transcriptional regulator (LTTR) OxyR. Extensive studies have focused on the classical Escherichia coli system to shed light on the mode of action of defensive weapons against oxidative stress. The underlying mechanism is mediated via the formation of redox-dependent disulfide bond between two conserved cysteines of OxyR, thus activating transcription of members of the OxyR regulon. However, only fragmentary information on the regulation and function of OxyR has been gleaned through genetic and biochemical analyses in the important opportunistic pathogen P. aeruginosa. In this report, we used a comprehensive transcriptional profiling analysis to delineate the OxyR regulon under three conditions (KingM-bM-^@M-^Ys A medium [Pseudomonas medium or PM], Luria Broth (LB), and LB when oxyR is overexpressed), to investigate its roles in different cellular aspects that are independent of the classical oxidative stress response. Interestingly, when grown in LB, OxyR was found to regulating many genes involved in the process of inter-cellular communication known as quorum sensing (QS). In contrast, when grown in PM, OxyR regulate the expression of a newly identified CSS (cell-surface signaling) system in an OxyR-dependent fashion. In addition, the results from oxyR overexpression further confirmed that OxyR was linked to regulation of QS and Type 3 Secretion (T3SS) in addition to the regulation of antioxidative genes. Taken together, our results show that, apart from its dominant role in defense against oxidative stress in P. aeruginosa, OxyR acts as a global regulator that provides a link between the regulation of oxidative stress response, QS and virulence. 15 samples, representing 5 different biological conditions, including 3 biological replicates for each condition

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The bacterial lifestyle that disguises stressful adaptations

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