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A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

ABSTRACT: Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both DeltaccpA and DeltacovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection.

SUBMITTER: Shelburne SA

PROVIDER: S-EPMC2841617 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

Shelburne Samuel A SA Olsen Randall J RJ Suber Bryce B Sahasrabhojane Pranoti P Sumby Paul P Brennan Richard G RG Musser James M JM

PLoS pathogens 20100319 3

Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulen ...[more]

PMID: 20333240

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Project description:Due to the immature gastrointestinal immune system, weaning piglets are highly susceptible to pathogens, e.g., enterotoxigenic Escherichia coli (ETEC). Generally, pathogens activate the immune cells (e.g., macrophages) and shape intracellular metabolism (including amino acid metabolism); nevertheless, the metabolic cues of tryptophan (especially melatonin pathway) in directing porcine macrophage function during ETEC infection remain unclear. Therefore, this study aimed to investigate the changes in the serotonin pathway of porcine macrophages during ETEC infection and the effect of melatonin on porcine macrophage functions. Porcine macrophages (3D4/21 cells) were infected with ETEC, and the change of serotonin pathway was analysed by reverse transcription PCR and metabolomic analysis. The effect of melatonin on porcine macrophage function was also studied with proteomic analysis. In order to investigate the effect of melatonin on bacterial clearance function of porcine macrophages during ETEC infection, methods such as bacterial counting, reverse transcription PCR and western blotting were used to detect the corresponding indicators. The results showed that ETEC infection blocked melatonin production in porcine macrophages (P < 0.05) which is largely associated with the heat-stable enterotoxin b (STb) of ETEC (P < 0.05). Interestingly, melatonin altered porcine macrophage functions, including bacteriostatic and bactericidal activities based on proteomic analysis. In addition, melatonin pre-treatment significantly reduced extracellular lactate dehydrogenase (LDH) activity (P < 0.05), indicating that melatonin also attenuated ETEC-triggered macrophage death. Moreover, melatonin pre-treatment resulted in the decrease of viable ETEC in 3D4/21 cells (P < 0.05), suggesting that melatonin enhances bacterial clearance of porcine macrophages. These results suggest that melatonin is particularly important in shaping porcine macrophage function during ETEC infection.

Dataset Information

A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

Publications

A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

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