A fatty acid binding protein of Streptococcuspneumoniae facilitates the acquisition of host polyunsaturated fatty acids

Research paper by Jessica M. Gullett, Maxime G. Cuypers, Matthew W. Frank, Stephen W. White, Charles O. Rock

Indexed on: 20 Sep '19Published on: 17 Sep '19Published in: Journal of Biological Chemistry


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) while bound by a fatty acid binding protein (FakB).  Staphylococcus aureus has two binding proteins while S. pneumoniae expresses three.  The functions of these binding proteins were not clear.  We determined the SpFakB1 and SpFakB2 binding proteins were bioinformatically related to the two binding proteins of S. aureus, and biochemical and X-ray crystallographic analysis showed that SpFakB1 selectively bound saturates while SpFakB2 akllows the activation of monounsaturates akin to their S. aureus counterparts.  The distinct SpFakB3 enables the utilization of polyunsaturates. The SpFakB3 crystal structure in complex with linoleic acid reveals an expanded fatty acid binding pocket within the hydrophobic interior of SpFakB3 that explains its ability to accommodate multiple cis double bonds. SpFakB3 also utilizes a different hydrogen bond network than other FakBs to anchor the fatty acid carbonyl and stabilize the protein. S. pneumoniae strain JMG1 (ΔfakB3) 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.