Streptococcus pneumoniae, S. pyogenes, and S. agalactiae membrane phospholipid remodeling in response to human serum

Abstract

Streptococcus pneumoniae, S. pyogenes (Group A Streptococcus; GAS), and S. agalactiae (Group B Streptococcus; GBS) are major etiological agents of diseases in humans. The cellular membrane, a crucial site in host-pathogen interactions, is poorly characterized in streptococci. Moreover, little is known about whether or how environmental conditions influence their lipid compositions. Using normal phase liquid chromatography coupled with electrospray ionization mass spectrometry, we characterized the phospholipids and glycolipids of S. pneumoniae, GAS, and GBS in routine undefined laboratory medium, streptococcal defined medium, and, in order to mimic the host environment, defined medium supplemented with human serum. In human serum-supplemented medium, all three streptococcal species synthesize phosphatidylcholine (PC), a zwitterionic phospholipid commonly found in eukaryotes but relatively rare in bacteria. We previously reported that S. pneumoniae utilizes the glycerophosphocholine (GPC) biosynthetic pathway to synthesize PC. Through substrate tracing experiments, we confirm that GAS and GBS scavenge lysoPC, a major metabolite in human serum, thereby using an abbreviated GPC pathway for PC biosynthesis. Furthermore, we found that plasmanyl-PC is uniquely present in the GBS membrane during growth with human serum, suggesting GBS possesses unusual membrane biochemical or biophysical properties. In summary, we report cellular lipid remodeling by the major pathogenic streptococci in response to metabolites present in human serum.