A fatty acid-binding protein of Streptococcus pneumoniae facilitates the acquisition of host polyunsaturated fatty acids.

Streptococcus pneumoniae is responsible for the majority of pneumonia, motivating ongoing searches for insights into its physiology that could enable new treatments. S. pneumoniae responds to exogenous fatty acids by suppressing its de novo biosynthetic pathway and exclusively utilizing extracellular fatty acids for membrane phospholipid synthesis. The first step in exogenous fatty acid assimilation is phosphorylation by fatty acid kinase (FakA), whereas bound by a fatty acid-binding protein (FakB). Staphylococcus aureus has two binding proteins, whereas S. pneumoniae expresses three. The functions of these binding proteins were not clear. We determined the Sp FakB1- and Sp FakB2-binding proteins were bioinformatically related to the two binding proteins of Staphylococcus aureus , and biochemical and X-ray crystallographic analysis showed that Sp FakB1 selectively bound saturates, whereas Sp FakB2 allows the activation of monounsaturates akin to their S. aureus counterparts. The distinct Sp FakB3 enables the utilization of polyunsaturates. The Sp FakB3 crystal structure in complex with linoleic acid reveals an expanded fatty acid-binding pocket within the hydrophobic interior of Sp FakB3 that explains its ability to accommodate multiple cis double bonds. Sp FakB3 also utilizes a different hydrogen bond network than other FakBs to anchor the fatty acid carbonyl and stabilize the protein. S. pneumoniae strain JMG1 (Δ fakB3 ) was deficient in incorporation of linoleate from human serum verifying the role of FakB3 in this process. Thus, the multiple FakBs of S. pneumoniae permit the utilization of the entire spectrum of mammalian fatty acid structures to construct its membrane.
(© 2019 Gullett et al.)