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

Lambert, Clara; Poullion, Thifaine; Zhang, Qiufen; Schmitt, Alain; Massé, Jean‐Marc; Gloux, Karine; Poyart, Claire; Fouet, Agnès

doi:10.1371/journal.pone.0284402

Cited by 4 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous observations identified multiple independent FabT point mutants harvested from the infection site of nonhuman primates, some of which mapped to His105 4 . A strain expressing a FabT H105Y point mutation was constructed in the reference strain M28PF1 (an emm28 strain, referred to as wild-type; WT) 11,12 , here called mFabT. The FabT His105 residue is in the middle of the α5 helix involved in dimerization and acyl-ACP binding (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…3b) 12 . degVSpy_1638 encodes an FA binding protein, of the FakB-family, which together with FakA constitutes a fatty acid kinase 12,20 . degVSpy_1638 is the only gene other than those comprising the FASII locus that is preceded by a FabT consensus DNA binding motif (5'-ANTTTGATTATCAAATT; Fig.…”

Section: Transcriptomes Of Mfabt Versus Wt Vary According To Efa Avai...mentioning

confidence: 99%

“…2b-c, Supplementary Fig. 3b) 12 . degVSpy_1638 encodes an FA binding protein, of the FakB-family, which together with FakA constitutes a fatty acid kinase 12,20 .…”

Section: Transcriptomes Of Mfabt Versus Wt Vary According To Efa Avai...mentioning

confidence: 99%

“…2c, Supplementary Table 4) 4 . In contrast, FASII genes, and a non-FASII gene within the FabT regulon (M28_Spy1638, encoding a putative fatty acid kinase binding protein; 13 ), remain transcriptionally active in the mFabT mutant, showing that FabT H105Y is defective for repression (Fig. 2e, Supplementary Table 4).…”

Section: Effects Of Fabt On Virulence Factor Expressionmentioning

confidence: 99%

“…2e) 21 . We recently reported that the degVSpy_1638 gene product is involved in endogenous FA storage or catabolism 12 .…”

Section: Transcriptomes Of Mfabt Versus Wt Vary According To Efa Avai...mentioning

confidence: 99%

See 4 more Smart Citations

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

Lambert,

Gaillard,

Wongdontree

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

In Streptococcus pyogenes, the fatty acid (FA) synthesis pathway FASII is feedback-controlled by the FabT repressor bound to an acyl-Acyl carrier protein. FabT defects are associated with attenuated virulence in animal models. Nevertheless, fabT point mutations arise in vivo. To resolve this paradox, we identified conditions and biotopes in which fabT behavior is defective, as being human tissues, cells, or cell filtrates. We then defined biotopes in which fabT mutants have a growth advantage, as being lipid rich. In a proof of concept we demonstrate that fabT mutants emerge in this context, due to FASII derepression, which prevents environmental FA incorporation. Energy dissipation is identified as the principal defect of fabT mutants, such that specific nutrients are consumed but do not promote growth. Our findings elucidate the nature of the link between FabT and virulence, provide a rationale for fabT mutant emergence, and identify the defect that causes attenuated fabT infection.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Transcriptomes Of Mfabt Versus Wt Vary According To Efa Avai...mentioning

confidence: 99%

“…2b-c, Supplementary Fig. 3b) 12 . degVSpy_1638 encodes an FA binding protein, of the FakB-family, which together with FakA constitutes a fatty acid kinase 12,20 .…”

Section: Transcriptomes Of Mfabt Versus Wt Vary According To Efa Avai...mentioning

confidence: 99%

Section: Effects Of Fabt On Virulence Factor Expressionmentioning

confidence: 99%

“…2e) 21 . We recently reported that the degVSpy_1638 gene product is involved in endogenous FA storage or catabolism 12 .…”

Section: Transcriptomes Of Mfabt Versus Wt Vary According To Efa Avai...mentioning

confidence: 99%

See 3 more Smart Citations

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

Lambert,

Gaillard,

Wongdontree

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

The double-edged role of FASII regulator FabT in Streptococcus pyogenes infection

Lambert,

Gaillard,

Wongdontree

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Acyl-AcpB, a FabT corepressor in Streptococcus pyogenes

Lambert,

d'Orfani,

Gaillard

et al. 2023

J Bacteriol

View full text Add to dashboard Cite

Membranes are a universal barrier to all cells. Phospholipids, essential bacterial membrane components, are composed of a polar head and apolar fatty acid (FA) chains. Most bacterial FAs are synthesized by the Type II FA synthesis pathway (FASII). In Streptococcaceae, Enterococci, and Lactococcus lactis , a unique feedback mechanism controls the FASII gene expression. FabT, encoded in the FASII main locus, is the repressor, and it is activated by long-chain acyl-acyl carrier protein (acyl-ACP). Many Streptococci, Enterococcus faecalis , but not L. lactis , possess two ACPs. The AcpA-encoding gene is within the FASII locus and is coregulated with the FASII genes. Acyl-AcpA is the end product of FASII. The AcpB-encoding gene is in operon with plsX encoding an acyl-ACP:phosphate acyltransferase. The role of acyl-AcpB as FabT corepressor is controversial. Streptococcus pyogenes , which causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections, possesses AcpB. In this study, by comparing the expression of FabT-controlled genes in an acpB -deleted mutant with those in a wild-type and in a fabT mutant strain, grown in the presence or absence of exogenous FAs, we show that AcpB is the S. pyogenes FabT main corepressor. Its deletion impacts membrane FA composition and bacterial adhesion to eucaryotic cells, highlighting the importance of FASII control. IMPORTANCE Membrane composition is crucial for bacterial growth or interaction with the environment. Bacteria synthesize fatty acids (FAs), membrane major constituents, via the Type II FAS (FASII) pathway. Streptococci control the expression of the FASII genes via a transcriptional repressor, FabT, with acyl-acyl carrier proteins (ACPs) as corepressor. Streptococcus pyogenes that causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections possesses two ACPs. acpA , but not acpB , is a FASII gene. In this study, we show that acyl-AcpBs are FabT main corepressors. Also, AcpB deletion has consequences on the membrane FA composition and bacterial adhesion to host cells. In addition to highlighting the importance of FASII control in the presence of exogeneous FAs for the adaptation of bacteria to their environment, our data indicate that FASII gene repression is mediated by a corepressor whose gene expression is not repressed in the presence of exogenous FAs.

show abstract

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

Cited by 4 publications

References 36 publications

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection

The double-edged role of FASII regulator FabT in Streptococcus pyogenes infection

Acyl-AcpB, a FabT corepressor in Streptococcus pyogenes

Contact Info

Product

Resources

About