AMPK in Pathogens.
During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host-pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3Bs-PT Government Associate Laboratory, Guimarães, Braga, Portugal.
Inês
I
Mesquita
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.|Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Diana
D
Moreira
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3Bs-PT Government Associate Laboratory, Guimarães, Braga, Portugal.
Belém
B
Sampaio-Marques
CNRS FR 3636, Université Paris Descartes, Paris, France.
Mireille
M
Laforge
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.|Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Anabela
A
Cordeiro-da-Silva
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3Bs-PT Government Associate Laboratory, Guimarães, Braga, Portugal.
Paula
P
Ludovico
CNRS FR 3636, Université Paris Descartes, Paris, France.|Centre de Recherche du CHU de Québec, Université Laval, Québec, QC, Canada.
Jérôme
J
Estaquier
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. ricardosilvestre@ecsaude.uminho.pt.|ICVS/3Bs-PT Government Associate Laboratory, Guimarães, Braga, Portugal. ricardosilvestre@ecsaude.uminho.pt.
Ricardo
R
Silvestre
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects / Q000276:immunology; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001424:Bacterial Infections / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000821:virology; D005658:Fungi / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009181:Mycoses / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000821:virology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014777:Virus Diseases / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000821:virology; D014780:Viruses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000890:Anti-Infective Agents; D021122:Protein Subunits; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
Bioenergetics; Host-pathogen interactions; Infection; Metabolism; Microbial auxotrophy; SNF1/AMPK