Bravo-Santano, Natalia, Ellis, James K., Mateos, Luis M., Calle, Yolanda, Keun, Hector C., Behrends, Volker ORCID: https://orcid.org/0000-0003-4855-5497 and Letek, Michal (2018) Intracellular Staphylococcus aureus Modulates Host Central Carbon Metabolism To Activate Autophagy. mSphere, 3 (4). ISSN 0099-2240

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Abstract

Staphylococcus aureus is a facultative intracellular pathogen that invades and replicates within many types of phagocytic and nonphagocytic cells. During intracellular infection, S. aureus is capable of subverting xenophagy and escaping to the cytosol of the host cell. Furthermore, drug-induced autophagy facilitates the intracellular replication of S. aureus, but the reasons behind this are unclear. Here, we have studied the host central carbon metabolism during S. aureus intracellular infection. We found extensive metabolic rerouting and detected several distinct metabolic changes that suggested starvation-induced autophagic flux in infected cells. These changes included increased uptake but lower intracellular levels of glucose and low abundance of several essential amino acids, as well as markedly upregulated glutaminolysis. Furthermore, we show that AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) phosphorylation levels are significantly increased in infected cells. Interestingly, while autophagy was activated in response to S. aureus invasion, most of the autophagosomes detected in infected cells did not contain bacteria, suggesting that S. aureus induces the autophagic flux during cell invasion for energy generation and nutrient scavenging. Accordingly, AMPK inhibition halted S. aureus intracellular proliferation.

Item Type:	Article
Identifier:	10.1128/mSphere.00374-18
Keywords:	Staphylococcus aureus, autophagy, host cell, intracellular pathogen, metabolism
Subjects:	Natural sciences > Cell and molecular biology Natural sciences
Depositing User:	Volker Behrends
Date Deposited:	29 Apr 2024 09:51
Last Modified:	29 Apr 2024 09:51
URI:	https://repository.uwl.ac.uk/id/eprint/11388

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