Feeding Uninvited Guests: mTOR and AMPK Set the Table for Intracellular Pathogens

Brunton, Jason; Steele, Shaun; Ziehr, Benjamin; Moorman, Nathaniel J.; Kawula, Thomas H.

doi:10.1371/journal.ppat.1003552

Cited by 55 publications

(56 citation statements)

References 31 publications

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“…Accordingly, AMPK and mTOR represent diverse yet versatile energy sensors and metabolic regulators that regulate cell fate decisions in eukaryotes. Consequently, pathogens may have evolved to manipulate these pathways in order to achieve optimal levels of proliferation and cell fitness while avoiding exhaustion of host resources (Brunton et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei

et al. 2016

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During infection in mammals, the protozoan parasite Trypanosoma brucei transforms from a proliferative bloodstream form to a quiescent form that is pre-adapted to host transition. AMP analogs are known to induce quiescence and also inhibit TbTOR4. To examine the role of AMP-activated kinase (AMPK) in regulation of this developmental transition, we characterized trypanosome TbAMPK complexes. Expression of a constitutively active AMPKα1 induces quiescence of the infective form and TbAMPKα1 phosphorylation occurs during differentiation of wild-type pleomorphic trypanosomes to the quiescent stumpy form in vivo. Compound C, a well-known AMPK inhibitor inhibits parasite differentiation in mice. We also provide evidence linking oxidative stress to TbAMPKα1 activation and quiescent differentiation, suggesting that TbAMPKα1 activation balances quiescence, proliferation and differentiation.

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Section: Introductionmentioning

confidence: 99%

The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei

et al. 2016

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“…Intracellular Brucella abortus also needs glucose for chronic infection (42). However, little is known about how extracellular bacterial pathogens access host metabolites (43). We observed that diabetic mice supported the growth of infecting V. vulnificus to higher levels than wild type mice (Fig.…”

Section: Discussionmentioning

confidence: 73%

Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo

Kim

Wen

et al. 2015

Journal of Biological Chemistry

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Background: Vibrio vulnficus produces SidC, an extracellular insulin-degrading enzyme. Results: SidC causes degradation of insulin, leading to proliferation of the pathogen, and sidC was expressed in low-glucose conditions. Conclusion: Degradation of insulin by SidC correlated with the proliferation of the pathogen. Significance: V. vulnificus manipulates host endocrine signals through SidC, making the host environment more favorable for its own proliferation.

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“…Activation of mTOR by HCV may enable the virus to orchestrate cell activities for the virus own benefit leading to HCV persistence and chronicity [33]. Through achieving significant viral protein translation and lipid production needed for virus assembly; leading to a steady-state of replication [34]. In the present study, the serum mTOR levels and intra-hepatic mTOR staining score were positively correlated with serum ALT, AST and the METAVIR histological activity grade and fibrosis stage in patients without HCC suggesting an association of mTOR activation with inflammation and fibrogenesis.…”

Section: Discussionmentioning

confidence: 99%

Target of Rapamycin (TOR) and Autophagy in Chronic Hepatitis C Virus Infection: Relation to Disease Activity

Lashen¹

2017

JLRDT

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Background: In chronic hepatitis C (CHC) infection, liver disease progression results from viral persistence. Deregulation of target of rapamycin (TOR) signaling and autophagy is detected in viral infections and cancer. We studied the role of TOR and autophagy in the progression of CHC infection.Methods: 54 patients infected with HCV, [27 with CHC; 13 with cirrhosis and 14 with hepatocellular carcinoma (HCC)]; and 15 healthy subjects were included. Quantification of serum TOR was determined using enzyme linked immunosorbent assay. Tissue samples were immune-stained using TOR and autophagy protein 5 (Atg5) polyclonal antibodies. Expression of TOR and Atg5 was scored semi-quantitatively.Results: Expression and serum TOR were higher in HCC patients compared to patients without HCC (P< 0.05). Serum and expression of TOR were positively correlated to inflammation, fibrosis, steatosis and tumor characteristics (Alpha-fetoprotein, maximum diameter, tumor grade and CLIP stage) (P<0.05). Expression of Atg5 was inversely correlated with inflammation, fibrosis and tumor characteristics (P<0.05), Atg5 showed significant inverse correlation with serum and intra-hepatic expression of TOR (P<0.05). Serum TOR showed high sensitivity and specificity in discriminating infected patients with and without HCC at a cut-off value of 4.55 ng/ml [Area under ROC curve = 0.970]. Conclusion:Activation of TOR plays an important role in progression of HCV related liver disease possibly though autophagy suppression and they could be a potential therapeutic target. Serum TOR is a potential seromarker in discriminating HCV infected patients with and without HCC with high sensitivity and specificity.

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Feeding Uninvited Guests: mTOR and AMPK Set the Table for Intracellular Pathogens

Cited by 55 publications

References 31 publications

The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei

The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei

Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo

Target of Rapamycin (TOR) and Autophagy in Chronic Hepatitis C Virus Infection: Relation to Disease Activity

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