Phosphatidylcholine Biosynthesis in Mitis Group Streptococci via Host Metabolite Scavenging

Joyce, Luke R.; Guan, Ziqiang; Palmer, Kelli L.

doi:10.1128/jb.00495-19

Cited by 35 publications

(86 citation statements)

References 72 publications

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“…The gene cdsA is required for the synthesis of CDP-DAG, which is then converted by PgsA to produce phosphatidylglycerophosphate (PGP), the immediate precursor of PG ( Fig. 1A) (18,41). We previously reported that cdsA deletion mutants of S. mitis and S. oralis do not synthesize PG, nor does a pgsA deletion mutant of SM43 (18, 41) ( (Table 1).…”

Section: Biosynthesis Of (Gro-p)-dihexosyl-dag Requires Phosphatidylgmentioning

confidence: 99%

“…Extraction of total lipids from stationary phase cells was performed by acidic Bligh-Dyer extraction as previously described (18). Specifically, cells were grown to stationary phase, The MS/MS analysis used nitrogen as the collision gas.…”

Section: Lipidomics Analysismentioning

confidence: 99%

“…We analyzed the type strain of S. mitis (ATCC 49456, referred to as SM61 hereafter), S. oralis (ATCC 35037), two clinically isolated S. pneumoniae strains (D39 and TIGR4), and Streptococcus sp. 1643 (referred to as SM43 hereafter), a human endocarditis isolate that was clinically identified as S. mitis but shares higher genomic identity with S. oralis (Table 1) (18,42). To confirm the possible monosaccharide identity of the DAG-linked sugars, in silico analyses were performed to identify orthologs of known glycolipid biosynthetic genes in the genomes of the tested strains.…”

Section: Introductionmentioning

confidence: 99%

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Streptococcus pneumoniae,S. mitis, andS. oralisproduce a phosphatidylglycerol-dependent,ltaS-independent glycerophosphate-linked glycolipid

Wei

Joyce

Wall

et al. 2020

Preprint

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Lipoteichoic acid (LTA) is a cell surface polymer of Gram-positive bacteria. LTA participates in host-microbe interactions including modulation of host immune reactions. It was previously reported that the major human pathogen Streptococcus pneumoniae and the closely related oral commensals S. mitis and S. oralis produce Type IV LTAs. Herein, using liquid chromatography/mass spectrometry (LC/MS)-based lipidomic analysis, we found that in addition to Type IV LTA biosynthetic precursors, S. mitis, S. oralis, and S. pneumoniae also produce glycerophosphate (Gro-P)-linked dihexosyl-diacylglycerol (DAG), which is a biosynthetic precursor of Type I LTA. Mutants in cdsA and pgsA produce dihexosyl-DAG but lack (Gro-P)-dihexosyl-DAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes. S. mitis, but neither S. pneumoniae nor S. oralis, encodes an ortholog of the PG-dependent Type I LTA synthase, ltaS. By heterologous expression analyses, we confirmed that S. mitis ltaS confers poly-(Gro-P) synthesis in both Escherichia coli and Staphylococcus aureus, and that S. mitis ltaS can rescue the severe growth defect of a S. aureus ltaS mutant. However, despite these observations, we do not detect a poly-(Gro-P) polymer in S. mitis using an anti-Type I LTA antibody. Moreover, (Gro-P)-linked dihexosyl-DAG is still synthesized by a S. mitis ltaS mutant, demonstrating that S. mitis LtaS does not catalyze the transfer of Gro-P from PG to dihexosyl-DAG. Finally, a S. mitis ltaS mutant has increased sensitivity to human serum, demonstrating that ltaS confers a beneficial but currently undefined function in S. mitis. Overall, our results demonstrate that S. mitis, S. pneumoniae, and S. oralis produce a (Gro-P)-linked glycolipid via a PG-dependent, ltaS-independent mechanism.

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Section: Biosynthesis Of (Gro-p)-dihexosyl-dag Requires Phosphatidylgmentioning

confidence: 99%

Section: Lipidomics Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Streptococcus pneumoniae,S. mitis, andS. oralisproduce a phosphatidylglycerol-dependent,ltaS-independent glycerophosphate-linked glycolipid

Wei

Joyce

Wall

et al. 2020

Preprint

Self Cite

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“…Since PC synthesis by the CDP-choline pathway is unique for certain species of Treponema [97], it is important to know the other pathways for PC synthesis that have been reported in prokaryotes. There are three other pathways for PC synthesis in bacteria (Figures 3(a)-3(c)) [54,84,86]. The PE methylation pathway (Figure 3(a)) [54,83], where PC is synthesized from PE in a sequence of three steps catalyzed by phospholipid N-methyltransferase (PLMT) with methyl donor S-adenosylmethionine (SAM) to form monomethylphosphatidylethanolamine (MMPE), dimethylphosphatidylethanolamine (DMPE), and then PC [54].…”

Section: Chok In Bacterial Lipid Biosynthetic Pathwaysmentioning

confidence: 99%

“…CDP-DAG on the other hand is produced from PA by CDP-DAG synthase [54] Secondly, the phosphatidylcholine synthase (Pcs) pathway (Figure 3(b)) [99] is comprised of a single step of condensing CDP-DAG with Cho by the Pcs enzyme [54,99]. Finally, the glycerophosphorylcholine (GPC) pathway (Figure 3(c)) [54,86] was reported only in X. campestris [98], S. mitis, and S. oralis [86]. In X. campestris, extracellular GPC is transported and converted via two-step acyl-CoAdependent acylation to lysophosphatidylcholine (LPC) by unknown enzymes and then to PC by acyltransferases Xc_ 0188 and Xc_0238 [98].…”

Section: Chok In Bacterial Lipid Biosynthetic Pathwaysmentioning

confidence: 99%

ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents

Khalifa

Few

Too

2020

BioMed Research International

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Novel antimicrobial agents are crucial to combat antibiotic resistance in pathogenic bacteria. Choline kinase (ChoK) in bacteria catalyzes the synthesis of phosphorylcholine, which is subsequently incorporated into the cell wall or outer membrane. In certain species of bacteria, phosphorylcholine is also used to synthesize membrane phosphatidylcholine. Numerous human ChoK inhibitors (ChoKIs) have been synthesized and tested for anticancer properties. Inhibition of S. pneumoniae ChoK by human ChoKIs showed a promising effect by distorting the cell wall and retarded the growth of this pathogen. Comparison of amino acid sequences at the catalytic sites of putative choline kinases from pathogenic bacteria and human enzymes revealed striking sequence conservation that supports the potential application of currently available ChoKIs for inhibiting bacterial enzymes. We also propose the combined use of ChoKIs and nanoparticles for targeted delivery to the pathogen while shielding the human host from any possible side effects of the inhibitors. More research should focus on the verification of putative bacterial ChoK activities and the characterization of ChoKIs with active enzymes. In conclusion, the presence of ChoK in a wide range of pathogenic bacteria and the distinct function of this enzyme has made it an attractive drug target. This review highlighted the possibility of “choking” bacterial ChoKs by using human ChoKIs.

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Recombinant and endogenous ways to produce methylated phospholipids in Escherichia coli

Kleetz

Vasilopoulos

Czolkoss

et al. 2021

Appl Microbiol Biotechnol

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Escherichia coli is the daily workhorse in molecular biology research labs and an important platform microorganism in white biotechnology. Its cytoplasmic membrane is primarily composed of the phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL). As in most other bacteria, the typical eukaryotic phosphatidylcholine (PC) is not a regular component of the E. coli membrane. PC is known to act as a substrate in various metabolic or catabolic reactions, to affect protein folding and membrane insertion, and to activate proteins that originate from eukaryotic environments. Options to manipulate the E. coli membrane to include non-native lipids such as PC might make it an even more powerful and versatile tool for biotechnology and protein biochemistry. This article outlines different strategies how E. coli can be engineered to produce PC and other methylated PE derivatives. Several of these approaches rely on the ectopic expression of genes from natural PC-producing organisms. These include PC synthases, lysolipid acyltransferases, and several phospholipid N-methyltransferases with diverse substrate and product preferences. In addition, we show that E. coli has the capacity to produce PC by its own enzyme repertoire provided that appropriate precursors are supplied. Screening of the E. coli Keio knockout collection revealed the lysophospholipid transporter LplT to be responsible for the uptake of lyso-PC, which is then further acylated to PC by the acyltransferase-acyl carrier protein synthetase Aas. Overall, our study shows that the membrane composition of the most routinely used model bacterium can readily be tailored on demand.Key points• Escherichia coli can be engineered to produce non-native methylated PE derivatives.• These lipids can be produced by foreign and endogenous proteins.• Modification of E. coli membrane offers potential for biotechnology and research. Graphical abstract

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Phosphatidylcholine Biosynthesis in Mitis Group Streptococci via Host Metabolite Scavenging

Cited by 35 publications

References 72 publications

Streptococcus pneumoniae,S. mitis, andS. oralisproduce a phosphatidylglycerol-dependent,ltaS-independent glycerophosphate-linked glycolipid

Streptococcus pneumoniae,S. mitis, andS. oralisproduce a phosphatidylglycerol-dependent,ltaS-independent glycerophosphate-linked glycolipid

ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents

Recombinant and endogenous ways to produce methylated phospholipids in Escherichia coli

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