Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection
Human skin is commonly colonized and infected by Staphylococcus aureus. Exactly how these organisms are sensed by keratinocytes has not been clearly delineated. Using a combination of metabolic and transcriptomic methodologies, we found that S. aureus infection is sensed as a metabolic stress by the...
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doaj-7742d5d0bcdc4bff8b4c93324a2a49742020-11-25T01:32:30ZengElsevierCell Reports2211-12472017-03-0118112742275110.1016/j.celrep.2017.02.055Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus InfectionMatthew Wickersham0Sarah Wachtel1Tania Wong Fok Lung2Grace Soong3Rudy Jacquet4Anthony Richardson5Dane Parker6Alice Prince7Deparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USADeparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USADeparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USADeparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USADeparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology & Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15260, USADeparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USADeparment of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USAHuman skin is commonly colonized and infected by Staphylococcus aureus. Exactly how these organisms are sensed by keratinocytes has not been clearly delineated. Using a combination of metabolic and transcriptomic methodologies, we found that S. aureus infection is sensed as a metabolic stress by the hypoxic keratinocytes. This induces HIF1α signaling, which promotes IL-1β production and stimulates aerobic glycolysis to meet the metabolic requirements of infection. We demonstrate that staphylococci capable of glycolysis, including WT and agr mutants, readily induce HIF1α responses. In contrast, Δpyk glycolytic mutants fail to compete with keratinocytes for their metabolic needs. Suppression of glycolysis using 2-DG blocked keratinocyte production of IL-1β in vitro and significantly exacerbated the S. aureus cutaneous infection in a murine model. Our data suggest that S. aureus impose a metabolic stress on keratinocytes that initiates signaling necessary to promote both glycolysis and the proinflammatory response to infection.http://www.sciencedirect.com/science/article/pii/S221112471730253XHIF1αkeratinocytesimmunometabolismglycolysisStaphylococcus aureus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew Wickersham Sarah Wachtel Tania Wong Fok Lung Grace Soong Rudy Jacquet Anthony Richardson Dane Parker Alice Prince |
spellingShingle |
Matthew Wickersham Sarah Wachtel Tania Wong Fok Lung Grace Soong Rudy Jacquet Anthony Richardson Dane Parker Alice Prince Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection Cell Reports HIF1α keratinocytes immunometabolism glycolysis Staphylococcus aureus |
author_facet |
Matthew Wickersham Sarah Wachtel Tania Wong Fok Lung Grace Soong Rudy Jacquet Anthony Richardson Dane Parker Alice Prince |
author_sort |
Matthew Wickersham |
title |
Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection |
title_short |
Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection |
title_full |
Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection |
title_fullStr |
Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection |
title_full_unstemmed |
Metabolic Stress Drives Keratinocyte Defenses against Staphylococcus aureus Infection |
title_sort |
metabolic stress drives keratinocyte defenses against staphylococcus aureus infection |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-03-01 |
description |
Human skin is commonly colonized and infected by Staphylococcus aureus. Exactly how these organisms are sensed by keratinocytes has not been clearly delineated. Using a combination of metabolic and transcriptomic methodologies, we found that S. aureus infection is sensed as a metabolic stress by the hypoxic keratinocytes. This induces HIF1α signaling, which promotes IL-1β production and stimulates aerobic glycolysis to meet the metabolic requirements of infection. We demonstrate that staphylococci capable of glycolysis, including WT and agr mutants, readily induce HIF1α responses. In contrast, Δpyk glycolytic mutants fail to compete with keratinocytes for their metabolic needs. Suppression of glycolysis using 2-DG blocked keratinocyte production of IL-1β in vitro and significantly exacerbated the S. aureus cutaneous infection in a murine model. Our data suggest that S. aureus impose a metabolic stress on keratinocytes that initiates signaling necessary to promote both glycolysis and the proinflammatory response to infection. |
topic |
HIF1α keratinocytes immunometabolism glycolysis Staphylococcus aureus |
url |
http://www.sciencedirect.com/science/article/pii/S221112471730253X |
work_keys_str_mv |
AT matthewwickersham metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT sarahwachtel metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT taniawongfoklung metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT gracesoong metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT rudyjacquet metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT anthonyrichardson metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT daneparker metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection AT aliceprince metabolicstressdriveskeratinocytedefensesagainststaphylococcusaureusinfection |
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