Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>

ABSTRACT The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. H...

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Autores principales:	Megan E. Ericson, Chitra Subramanian, Matthew W. Frank, Charles O. Rock
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Staphylococcus aureus fatty acid hemolysin phospholipid two-component regulatory systems virulence factors Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1791429d5b0143d89a786bd6199ca655
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spelling	oai:doaj.org-article:1791429d5b0143d89a786bd6199ca6552021-11-15T15:51:44ZRole of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>10.1128/mBio.00988-172150-7511https://doaj.org/article/1791429d5b0143d89a786bd6199ca6552017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00988-17https://doaj.org/toc/2150-7511ABSTRACT The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. IMPORTANCE The SaeRS two-component system is a master transcriptional activator of virulence factor production in response to the host environment in S. aureus, and strains lacking FA kinase have severely attenuated SaeRS-dependent virulence factor transcription. FA kinase is required for the activation of exogenous FAs, and it plays a role in cellular lipid homeostasis by recycling cellular FAs into the phospholipid biosynthetic pathway. Activation of the sensor kinase, SaeS, is mediated by its membrane anchor domain, and the FAs which accumulate in FA kinase knockout strains are potent inhibitors of SaeS-dependent signaling. This work identifies FAs as physiological effectors for the SaeRS system and reveals a connection between cellular lipid homeostasis and the regulation of virulence factor transcription. FA kinase is widely distributed in Gram-positive bacteria, suggesting similar roles for FA kinase in these organisms.Megan E. EricsonChitra SubramanianMatthew W. FrankCharles O. RockAmerican Society for MicrobiologyarticleStaphylococcus aureusfatty acidhemolysinphospholipidtwo-component regulatory systemsvirulence factorsMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus fatty acid hemolysin phospholipid two-component regulatory systems virulence factors Microbiology QR1-502
spellingShingle	Staphylococcus aureus fatty acid hemolysin phospholipid two-component regulatory systems virulence factors Microbiology QR1-502 Megan E. Ericson Chitra Subramanian Matthew W. Frank Charles O. Rock Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>
description	ABSTRACT The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. IMPORTANCE The SaeRS two-component system is a master transcriptional activator of virulence factor production in response to the host environment in S. aureus, and strains lacking FA kinase have severely attenuated SaeRS-dependent virulence factor transcription. FA kinase is required for the activation of exogenous FAs, and it plays a role in cellular lipid homeostasis by recycling cellular FAs into the phospholipid biosynthetic pathway. Activation of the sensor kinase, SaeS, is mediated by its membrane anchor domain, and the FAs which accumulate in FA kinase knockout strains are potent inhibitors of SaeS-dependent signaling. This work identifies FAs as physiological effectors for the SaeRS system and reveals a connection between cellular lipid homeostasis and the regulation of virulence factor transcription. FA kinase is widely distributed in Gram-positive bacteria, suggesting similar roles for FA kinase in these organisms.
format	article
author	Megan E. Ericson Chitra Subramanian Matthew W. Frank Charles O. Rock
author_facet	Megan E. Ericson Chitra Subramanian Matthew W. Frank Charles O. Rock
author_sort	Megan E. Ericson
title	Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>
title_short	Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>
title_full	Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>
title_fullStr	Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>
title_full_unstemmed	Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>
title_sort	role of fatty acid kinase in cellular lipid homeostasis and saers-dependent virulence factor expression in <italic toggle="yes">staphylococcus aureus</italic>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/1791429d5b0143d89a786bd6199ca655
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Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in <italic toggle="yes">Staphylococcus aureus</italic>

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