Cellular membranes typically comprise a lipid bilayer composed of a polar head and an apolar body of fatty acids (FAs). The structure and length of the FAs are critical for membrane topology and properties such as fluidity, permeability and integrity. These characteristics are crucial for the adaptation of bacteria to various environments. Most bacteria synthesize FAs through the FASII fatty acid synthesis pathway. This pathway is not essential in Gram-positive bacteria that use exogenous FAs to synthesize their lipids. The incorporation of exogenous FAs into the lipids of Gram-positive bacteria involves a Fatty Acid kinase (Fak) complex that phosphorylates exogenous FAs, producing acyl-PO4. Acyl-PO4 is a substrate of the lipid biosynthetic pathway. The Fak complex is composed of two proteins, FakA provides the kinase activity and interacts with the FA-binding FakB proteins. Firmicutes have two or three fakB genes, the FakB proteins allowing the incorporation of saturated or unsaturated FA. A few rare species, including Streptococcus pyogenes, have four FakBs, the role of the fourth one being unknown.
S. pyogenes, also known as group A streptococcus (GAS), causes mild infections, but also severe, invasive infections and post-infectious sequelae. GAS is responsible for more than 500,000 deaths per year worldwide. Since 2019, there has been a resurgence of mild and fatal GAS infections in Europe.
To decipher the role of the fourth FakB, named FakB4, researchers determined its gene expression. Unlike the other FakB proteins, FakB4 synthesis is repressed in the presence of exogenous FAs. This suggests that its role is related to endogenous FAs. The authors also constructed a mutant strain that no longer produces FakB4. They compared the FA and lipid content of the membranes of the parental wild-type and the mutant strain. The deletion of FakB4 has no impact on the percentage of different lipids present. However, the mutant strain in FakB4 produces more lipids and more extracellular membrane vesicles than the wild-type strain. This indicates that FakB4 binds endogenous FAs and does not transfer them to the lipid biosynthetic pathway. FakB4 can either store them or drive them to a catabolic pathway that remains to be defined. Excess FA is toxic to bacteria. Detoxification mechanisms have been described, but most are absent in S. pyogenes. Thus, FakB4, by scavenging these FAs, would annihilate the toxicity without requiring their export.
Legend: In contrast to FakB1, 2 and 3, which allow the incorporation of exogenous fatty acids into the membrane of S. pyogenes, FakB4 allows the storage or catabolism of supernumerary endogenous fatty acids. © Agnès Fouet, Clara Lambert
Overall, this study indicates that the activities of FakB4, on the one hand, and the other three FakB proteins, on the other hand, are involved under different growth conditions. Thus, these proteins target FAs of different origins and play different roles, that of FakB4 having never been described before.
Vignette : © Clara Lambert et Alain Schmitt
To learn more
Lambert C, Poullion T, Zhang Q, Schmitt A, Masse J-M, Gloux K, et al. (2023) A Streptococcus pyogenes DegV protein regulates the membrane lipid content and limits the formation of extracellular vesicles. PLoS ONE 18(4): e0284402. https://doi.org/10.1371/journal. pone.0284402