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NMR-Metabolomics Shows That BolA Is an Important Modulator of Salmonella Typhimurium Metabolic Processes under Virulence Conditions.

ABSTRACT: BolA is a ubiquitous global transcription factor. Despite its clear role in the induction of important stress-resistant physiological changes and its recent implication in the virulence of Salmonella, further research is required to shed light on the pathways modulated by BolA. In this study, we resorted to untargeted 1H-NMR metabolomics to understand the impact of BolA on the metabolic profile of Salmonella Typhimurium, under virulence conditions. Three strains of S. Typhimurium SL1344 were studied: An SL1344 strain transformed with an empty plasmid (control), a bolA knockout mutant (?bolA), and a strain overexpressing bolA (bolA+). These strains were grown in a minimal virulence-inducing medium and cells were collected at the end of the exponential and stationary phases. The extracts were analyzed by NMR, and multivariate and univariate statistical analysis were performed to identify significant alterations. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) of 1H-NMR data allowed the discrimination between the metabolic profiles of these strains, revealing increased levels of acetate, valine, alanine, NAD+, succinate, coenzyme A, glutathione, and putrescine in bolA+. These results indicate that BolA regulates pathways related to stress resistance and virulence, being an important modulator of the metabolic processes needed for S. Typhimurium infection.

SUBMITTER: Graca-Lopes G

PROVIDER: S-EPMC6918366 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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NMR-Metabolomics Shows That BolA Is an Important Modulator of Salmonella Typhimurium Metabolic Processes under Virulence Conditions.

Graça-Lopes Gil G Graça Gonçalo G Barahona Susana S Moreira Ricardo N RN Arraiano Cecília M CM Gonçalves Luís G LG

Metabolites 20191023 11

BolA is a ubiquitous global transcription factor. Despite its clear role in the induction of important stress-resistant physiological changes and its recent implication in the virulence of Salmonella, further research is required to shed light on the pathways modulated by BolA. In this study, we resorted to untargeted 1H-NMR metabolomics to understand the impact of BolA on the metabolic profile of Salmonella Typhimurium, under virulence conditions. Three strains of S< ...[more]

PMID: 31652780

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Project description:The intracellular pathogen Salmonella enterica serovar Typhimurium has emerged as a major cause of foodborne illness, representing a severe clinical and economic concern worldwide. The capacity of this pathogen to efficiently infect and survive inside the host depends on its ability to synchronize a complex network of virulence mechanisms. Therefore, the identification of new virulence determinants has become of paramount importance in the search of new targets for drug development. BolA-like proteins are widely conserved in all kingdoms of life. In Escherichia coli, this transcription factor has a critical regulatory role in several mechanisms that are tightly related to bacterial virulence. Therefore, in the present work we used the well-established infection model Galleria mellonella to evaluate the role of BolA protein in S Typhimurium virulence. We have shown that BolA is an important player in S Typhimurium pathogenesis. Specifically, the absence of BolA leads to a defective virulence capacity that is most likely related to the remarkable effect of this protein on S Typhimurium evasion of the cellular response. Furthermore, it was demonstrated that BolA has a critical role in bacterial survival under harsh conditions since BolA conferred protection against acidic and oxidative stress. Hence, we provide evidence that BolA is a determining factor in the ability of Salmonella to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence.IMPORTANCE BolA has been described as an important protein for survival in the late stages of bacterial growth and under harsh environmental conditions. High levels of BolA in stationary phase and under stresses have been connected with a plethora of phenotypes, strongly suggesting its important role as a master regulator. Here, we show that BolA is a determining factor in the ability of Salmonella to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. This work constitutes a relevant step toward an understanding of the role of BolA protein and may have an important impact on future studies in other organisms. Therefore, this study is of utmost importance for understanding the genetic and molecular bases involved in the regulation of Salmonella virulence and may contribute to future industrial and public health care applications.

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NMR-Metabolomics Shows That BolA Is an Important Modulator of Salmonella Typhimurium Metabolic Processes under Virulence Conditions.

Publications

NMR-Metabolomics Shows That BolA Is an Important Modulator of <i>Salmonella</i> Typhimurium Metabolic Processes under Virulence Conditions.

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