FabT, a Bacterial Transcriptional Repressor That Limits Futile Fatty Acid Biosynthesis

Lambert, Clara; Poyart, Claire; Gruss, Alexandra; Fouet, Agnès

doi:10.1128/mmbr.00029-22

Cited by 19 publications

(24 citation statements)

References 51 publications

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“…The synthesis of lipids is an intricate process regulated by multiple enzymes. Among these, FAS is a vital participant mainly contributing to fatty acid synthesis and its functional characterization has been reported in bacteria [ 18 ] and fungi [ 19 ]. However, the identification and characterization of FAS in insects have still received less attention.…”

Section: Discussionmentioning

confidence: 99%

The Key Role of Fatty Acid Synthase in Lipid Metabolism and Metamorphic Development in a Destructive Insect Pest, Spodoptera litura (Lepidoptera: Noctuidae)

Song

Liu

et al. 2022

IJMS

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Fatty acid synthase (FAS) is a key enzyme in the lipid synthesis pathway, however, its roles in insects remain largely unknown. Here, we firstly identified two FAS genes from the transcriptome dataset of the general cutworm Spodoptera litura, which is a destructive insect pest of many crops. Both SlFAS1 and SlFAS2 were highly expressed in third instar larvae and in their fat bodies. Then, we successfully silenced SlFAS1 in third instar larvae and the content of α-linolenic acid and triglyceride was significantly decreased. Besides that, the effect of FAS on the metamorphic development in S. litura was evaluated. The results indicate that after silencing SlFAS1, the survival rates of S. litura larvae decreased significantly compared to the control groups. Silencing SlFAS1 in fifth instar larvae resulted in more malformed pupae and adults, and the emergence rates were significantly reduced. Furthermore, the ecdysone content in the haemolymph of fifth instar larvae was significantly decreased after silencing SlFAS1. In addition, knocking down SlFAS1 significantly alters the expression of other key genes in the lipogenesis pathway, implying that FAS has an impact on the lipogenesis pathway. The present study deepens the understanding of FAS in insects and provides novel potential targets for managing insect pests.

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Section: Discussionmentioning

confidence: 99%

The Key Role of Fatty Acid Synthase in Lipid Metabolism and Metamorphic Development in a Destructive Insect Pest, Spodoptera litura (Lepidoptera: Noctuidae)

Song

Liu

et al. 2022

IJMS

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“…FabT is present in streptococci, enterococci and lactococci. FabT belongs to the MarR family of regulators [for review, [ 16 ]]. The expression of the other fakB genes is not controlled by FabT in the M1 strain [ 15 ] and a FASII coregulation may shed light on the function of the protein.…”

Section: Resultsmentioning

confidence: 99%

“…We hypothesized that fakB4 may be directly controlled by FabT. Consensus FabT binding sequences are found along the FASII locus, which includes fabT [[ 16 ], and references herein]. We sought whether one was also present downstream from the fakB4 transcription start site previously described [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

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A Streptococcus pyogenes DegV protein regulates the membrane lipid content and limits the formation of extracellular vesicles

et al. 2023

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Membranes contain lipids that are composed of fatty acids (FA) and a polar head. Membrane homeostasis is crucial for optimal bacterial growth and interaction with the environment. Bacteria synthesize their FAs via the FASII pathway. Gram-positive bacteria can incorporate exogenous FAs which need to be phosphorylated to become substrate of the lipid biosynthetic pathway. In many species including staphylococci, streptococci and enterococci, this phosphorylation is carried out by the Fak complex, which is composed of two subunits, FakA and FakB. FakA is the kinase. FakB proteins are members of the DegV family, proteins known to bind FAs. Two or three FakB types have been identified depending on the bacterial species and characterized by their affinity for saturated and/or unsaturated FAs. Some species such as Streptococcus pyogenes, which causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections, possess an uncharacterized additional DegV protein. We identify here this DegV member as a fourth FakB protein, named FakB4. The fakB4 gene is co-regulated with FASII genes suggesting an interaction with endogenous fatty acids. fakB4 deletion has no impact on membrane phospholipid composition nor on the percentage of other major lipids. However, the fakB4 mutant strain produced more lipids and more extracellular membrane vesicles than the wild-type strain. This suggests that FakB4 is involved in endogenous FA binding and controls FA storage or catabolism resulting in a limitation of extracellular FA release via membrane vesicles.

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“…Furthermore, proteomic analysis indicated that exposure to a low concentration of H5−23 (1/2× MIC) led to a significant upregulation of proteins (fabZ1, fabI, fabG, and accD) associated with fatty acid metabolism and synthesis pathways. 28,29 Interestingly, the nonphosphorylated form of YycF inhibits the transcription of the fabT repressor and controls the fatty acid biosynthesis in Streptococcus pneumoniae by regulating the expression of fab genes. 30,31 These findings suggest a potential interplay among membrane metabolism, fatty acid metabolism, and the YycFG TCS signaling pathway.…”

Section: Synergistic Effect Of H5−23 In Combination Withmentioning

confidence: 99%

Thiazolopyrimidinone Derivative H5–23 Enhances Daptomycin Activity against Linezolid-Resistant Enterococcus faecalis by Disrupting the Cell Membrane

Xiong,

Chen,

Bai

et al. 2023

ACS Infect. Dis.

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FabT, a Bacterial Transcriptional Repressor That Limits Futile Fatty Acid Biosynthesis

Cited by 19 publications

References 51 publications

The Key Role of Fatty Acid Synthase in Lipid Metabolism and Metamorphic Development in a Destructive Insect Pest, Spodoptera litura (Lepidoptera: Noctuidae)

The Key Role of Fatty Acid Synthase in Lipid Metabolism and Metamorphic Development in a Destructive Insect Pest, Spodoptera litura (Lepidoptera: Noctuidae)

A Streptococcus pyogenes DegV protein regulates the membrane lipid content and limits the formation of extracellular vesicles

Thiazolopyrimidinone Derivative H5–23 Enhances Daptomycin Activity against Linezolid-Resistant Enterococcus faecalis by Disrupting the Cell Membrane

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