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

Abstract

Streptococcus pneumoniae , S. pyogenes (Group A Streptococcus ; GAS) and S. agalactiae (Group B Streptococcus ; GBS) are major aetiological 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 MS, 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 remodelling by the major pathogenic streptococci in response to metabolites present in human serum.

Identification of a novel cationic glycolipid in Streptococcus agalactiae that contributes to brain entry and meningitis

“…the observation that glucosyl-diacylglycerol (Glc-DAG) is a major membrane component of GBS and other streptococci [14] and results from an isotopic labeling experiment using 13 Clabeled glucose (Glucose-13 C 6 ). The assignment of lysine modification was supported by an isotopic labeling experiment with deuterated lysine (lysine-d4).…”

“…The assignment of lysine modification was supported by an isotopic labeling experiment with deuterated lysine (lysine-d4). The expected mass shifts (+4 Da) were observed in both molecular ions and MS/MS product ions (S2 Fig) . Comparison of both MS/MS spectra of labeled (Glucose- 13…”

“…Comparatively, little is known about GBS cellular membrane lipids. To our knowledge, the only characterization of GBS lipids prior to our current study was the identification of the phospholipids phosphatidylglycerol (PG), cardiolipin (CL), and lysyl-phosphatidylglycerol (Lys-PG) in GBS [11][12][13]. Similarly, investigation into the glycolipids of the GBS membrane has focused on di-glucosyl-diacylglycerol (Glc 2 -DAG), which is the lipid anchor of the Type I lipoteichoic acid, and its role in pathogenesis [14].…”

Microbial Musings – May 2021

“…The next article that took my eye was from the group of Microbiology Editor Kelli Palmer (@palmer_lab) at the University of Texas, Dallas, USA, continuing the publications of graduate student Luke Joyce (@Luke_Boitjie) [10]. The authors are interested in the dynamics of the membrane lipid composition of pathogenic streptococci, the investigation of which through lipidomics is still one of final frontiers of fundamental cell biology outside of model bacteria.…”

“…In this study they expand the work to the other two major types of pathogenic streptococci, namely group A streptococci (GAS) and Streptococcus agalactiae (group B streptococci; GBS) and find that, as with S. pneumoniae , no PC is seen in the membrane in cells grown on minimal medium, but also not on the Todd–Hewitt media, although it was detected when human serum was added [10]. They surmise that these species can scavenge another form of PC called lyso-PC, which is known to be present in serum, and then modify this to add PC into their own membrane.…”