Phosphatidylcholine biosynthesis in Mitis group streptococci via host metabolite scavenging

Abstract

14The Mitis group streptococci include the major human pathogen Streptococcus 15 pneumoniae and the oral opportunistic pathogens S. mitis and S. oralis which are 16 primary colonizers in the oral cavity and agents of bacteremia and infective endocarditis 17 in immunocompromised patients. Bacterial membrane lipids play crucial roles in 18 microbe-host interactions, yet for many pathogens, the composition of the membrane is 19 poorly understood. In this study, we characterized the lipidomes of selected species of 20 Mitis group streptococci and investigated the mechanistic basis for biosynthesis of the 21 phospholipid phosphatidylcholine (PC). PC is a major lipid in eukaryotic cellular 22 membranes, but it is considered to be comparatively rare in bacterial taxa. Using liquid 23 chromatography/mass spectrometry (LC/MS) in conjunction with stable isotope tracing, 24 we determined that Mitis group streptococci synthesize PC via the rare host metabolite 25 scavenging pathway, the glycerophosphocholine (GPC) pathway, which is largely 26 uncharacterized in bacteria. Furthermore, we identify the acyltransferase, PlsC, as 27 playing a major role in the pathway by acylating lysoPC to PC. Our work demonstrates 28 that Mitis group streptococci including S. pneumoniae remodel their membrane in 29 response to the major human metabolites GPC and lysoPC. 30 31 Key words 32 33 Phosphatidylcholine, phospholipid, Streptococcus pneumoniae, Streptococcus mitis, 34 Streptococcus oralis, Mitis group streptococci, glycerophosphocholine 35 3 36 Significance 37 38We lack fundamental information about the structure of the cellular membrane even for 39 the best studied pathogens of critical significance for human health. The Mitis group 40 streptococci are closely linked to humans in health and disease. Here, we demonstrate 41 that these streptococci scavenge major human metabolites and use them to synthesize 42 the membrane phospholipid phosphatidylcholine. Our work is significant because it 43 identifies a mechanism by which the major human pathogen S. pneumoniae and the 44 primary human oral colonizers S. mitis and S. oralis remodel their membrane in 45 response to the host.46 48 The Mitis group streptococci are Gram-positive bacteria that natively inhabit the human 49 oral cavity, nasopharynx, and gastrointestinal tract (1). They include the species S. mitis 50 and S. oralis, which are among the first colonizers of the human oral cavity from birth 51 and are believed to play important roles in host-microbe-microbe interactions by 52 creating an anchor for biofilm formation with other oral microbiota (2, 3). They are also 53 opportunistic pathogens causing bacteremia and infective endocarditis (4-7). They also 54 include the major human pathogen, S. pneumoniae. S. pneumoniae has >99% 16S 55 rRNA sequence identity with S. mitis and S. oralis (8-10), and with which they 56 exchange capsule biosynthesis and antibiotic resistance genes (11, 12) and show 57 antibody cross-reactivity (13). 58 59 We, and others, recently reported that Mit...

Streptococcus Pneumoniae Teichoic Acids

“…pneumoniae TAs is decorated with a large number of phosphorylcholine residues. The bacterial wall surface proteins, collectively known as choline-binding proteins (CBP) family proteins, are noncovalently bound to the phosphocholine of the teichoic acid and anchored to the TAs [18][19][20] . CBP is the family of polypeptides found in pneumococci and related species and some of their associated phages, it is mainly involved in immune escape, virulence and host pathogenicity [11,21] .…”