In Streptococcus pyogenes, acyl-AcpB is a major co-repressor of FabT, the transcriptional repressor of the fatty acid biosynthetic pathway

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Bacteria synthesize fatty acids, the main constituents of the membrane, via the FASII pathway. In streptococci, the FabT transcriptional repressor controls FASII gene expression. Its co-repressor is acyl-ACP (Acyl Carrier Protein). Streptococcus pyogenes, which causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections, has two ACPs. Unlike acpA, acpB is not a FASII pathway gene.

Claire Poyart and Agnès Fouet's team has shown that acyl-AcpB is the main corepressor of FabT. Thus, FASII gene repression is mediated by a co-repressor whose synthesis is not repressed in the presence of exogenous fatty acids. In addition, deletion of acpB affects membrane fatty acid composition and bacterial adhesion to host cells. AcpB is thus involved in the interaction of bacteria with their environment.

Cell membranes generally comprise a lipid bilayer consisting of a polar head and apolar fatty acid chains (FAs). The structure and length of the FAs determine the topology and properties of the membrane. This is crucial for the adaptation of bacteria to different environments. Most bacteria synthesize FAs via the FASII FA synthesis pathway. This pathway is not essential in Gram-positive bacteria, which use exogenous FAs to synthesize their lipids. In lactic acid bacteria, the FASII pathway is controlled by the transcriptional repressor FabT via a feedback mechanism; FabT has acyl-ACP (Acyl Carrier Protein) as a co-repressor. Their effectiveness depends on the length and saturation of the acyls. ACP can also vary: some Streptococci and Enterococci have two genes encoding ACP. One, acpA, belongs to the FASII locus and, like FASII genes, is repressed in the presence of exogenous FAs. The other, acpB, is in operon with plsX, PlsX being involved in phospholipid biosynthesis, and is not repressed in the presence of exogenous FAs. The role of AcpB as a co-repressor of FabT is controversial. The authors chose to study it in Streptococcus pyogenes, which possesses both AcpA and AcpB.

S. pyogenes, also known as Group A Streptococcus (GAS), causes mild infections, but also severe, invasive infections and post-infectious sequelae. S. pyogenes is responsible for over 500,000 deaths worldwide every year. Since 2019, there has been a resurgence of benign and fatal S. pyogenes infections in Europe.

To determine the role of AcpB, the researchers created an acpB gene-deleted mutant (DAcpB) and characterized different phenotypes. They also constructed a mutant in fabT (mFabT) and compared the two mutant strains. Whether AcpB is involved in the control of the FASII pathway was tested by analysis of the repression of FASII gene expression in the presence of exogenous FAs using qRT-PCR. The DAcpB strain has largely lost this ability. Thus, AcpB is a major co-repressor of FabT. Comparison of FASII gene expression in the two mutant strains shows that the effect of acpB deletion is less significant than that of a point mutation in fabT. This indicates that AcpB is not the only co-repressor, suggesting that AcpA may also play this role in S. pyogenes. The consequences of this deregulation on the bacterial membrane were characterized by determining the FA composition of membranes. The FAs of the DAcpB strain are longer and more saturated than those of the wild-type strain. This is due, on the one hand, to deregulation of the FASII pathway and, on the other, to the fact that the gene encoding the enzyme catalyzing FA unsaturation is less derepressed than those encoding the last elongation steps. Comparison of the membrane composition of the DAcpB and mFabT strains shows that FA synthesis is more affected in the latter. his reflects the difference in regulation observed. Finally, as surface structures are involved in adhesion to host cells, the researchers analyzed this for both strains. The DAcpB strain shows a defect in adhesion to epithelial cells. The same applies to the mFabT strain, with no significant difference in adhesion between the two strains. Thus, modification of the membrane composition of the DAcpB strain, although weaker than that of the mFabT strain, is sufficient to impair adhesion to eukaryotic cells.

In conclusion, in the presence of long-chain unsaturated FAs, acyl-AcpB are the major co-repressors of FabT in S. pyogenes. Biochemical experiments had shown the same to be true in Streptococcus pneumoniae. However, this cannot be generalized to all Streptococci, as some strains of Streptococcus agalactiae, for example, lack the acpB gene. Finally, in S. pyogenes, a deletion of acpB, through the contribution of AcpB to the regulation of FASII transcription by FabT, weakens bacterial adhesion to host cells, confirming the importance of FASII regulation for bacterial interaction with the host.

Copyright figure : Clara Lambert.


Lambert C., d’Orfani A., Gaillard M., Zhang Q., Gloux K., Poyart C., Fouet A. Acyl-AcpB, a FabT co-repressor in Streptococcus pyogenesJ. Bacteriol., 9 Oct. 2023. PMID: 37811985


Agnès Fouet

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