Dataset Information

Stress-Induced Iron-Sulfur Cluster Damage as a Conserved Trigger of the Stringent Response

ABSTRACT: Pathogenic bacteria rely on the stringent response to adapt to hostile environments encountered within the host. However, the mechanisms by which host-induced stress activates this response remain poorly understood. Here, we identify iron-sulfur (Fe-S) cluster damage as a conserved trigger of the stringent response in major Gram-negative pathogens, including Salmonella enterica, Enterobacter cloacae, and Klebsiella pneumoniae. We demonstrate that Fe-S cluster disruption—triggered by oxidative stress or metal imbalance—limits intracellular pools of sulfur-containing and branched-chain amino acids, thereby activating the (p)ppGpp synthetase RelA. We further show that during Fe-S cluster stress, (p)ppGpp plays a dual role: enhancing bacterial fitness and promoting virulence by upregulating the Salmonella SPI-2 type III secretion system. These findings reveal a conserved mechanism by which pathogenic bacteria integrate host-associated stresses into an adaptive transcriptional response that promotes fitness and virulence, highlighting Fe-S cluster integrity as a central hub for environmental sensing during infection.

ORGANISM(S): Salmonella enterica subsp. enterica serovar Typhimurium

PROVIDER: GSE305564 | GEO | 2025/08/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatory network providing rapid adaptation to a variety of growth-affecting stress conditions such as nutrient deficiency, is essential for replication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions. cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wild-type and rsh mutant in a synthetic minimal medium, partially mimicking the nutrient-poor environment of the intramacrophagic vacuole. A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 52% were up-regulated and 48% were down-regulated. The pleiotropic character of the response was confirmed, as the genes encoded factors belonging to various functional groups, comprising an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems, and energy metabolism proteins. Several virulence genes were under the positive control of (p)ppGpp. Methionine was the only amino acid whose biosynthesis was absolutely dependent on stringent response in B. suis. The study illustrated the complexity of the processes involved in adaptation to nutrient starvation, and contributed to a better understanding of the correlation between stringent response and Brucella virulence. Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responses playing a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress. Two-condition experiment, wild-type against rsh mutant. Biological replicates: 4 wild-type, 4 rsh mutant, independently grown in minimal medium (under nutrient starvation condition) and harvested. One replicate per array. Please note that Channel 1 (Cy3) on each hybridization was a universal reference (Uref) used as a reference point to merge two (2 channel arrays) into a virtual 2 channel array with wild-type versus rsh mutant.

Dataset Information

Stress-Induced Iron-Sulfur Cluster Damage as a Conserved Trigger of the Stringent Response

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets