Plasma Lipidomics of Tuberculosis Patients: Altered Phosphatidylcholine Remodeling

Wood, Paul L.; Tippireddy, Soumya; Feriante, Joshua

doi:10.4155/fsoa-2017-0011

Cited by 9 publications

(7 citation statements)

References 15 publications

(17 reference statements)

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“…Previous studies have demonstrated that the level of plasma lysophosphatidylcholine (LPC) in patients with TB significantly decreased. 25 , 26 Consistent with these results, we also found that a variety of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) decreased significantly in the plasma of untreated patients with TB, while restored to the normal level in patients achieved cure after intensive treatment.…”

Section: Discussionsupporting

confidence: 77%

Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients

Chen

Han

Zhang

et al. 2021

Sig Transduct Target Ther

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Currently, the management of pulmonary tuberculosis (TB) lacks potent medications and accurate efficacy evaluation biomarkers. In view of the fact that the host lipids are the important energy source of Mycobacterium tuberculosis (Mtb), UPLC-MS/MS based on lipid metabolism was used to monitor the plasma lipid spectrum of TB patients from the initial diagnosis to cured. The analysis showed that TB patients presented aberrant metabolism of phospholipids, glycerides, and sphingolipids. Upon the treatment, the abnormal expression of Cer (d18:1/24:0), CerP (d18:1/20:3), LPE (0:0/22:0), LPA (0:0/16:0), and LPA (0:0/18:0) in TB patients were gradually normalized, indicating that the intervention of lipid metabolism could block energy metabolism and inhibit the cell wall synthesis of Mtb. Furthermore, the increase in ceramide (Cer) levels could promote autophagosome–lysosome fusion. LPA (0:0/16:0) and LPA (0:0/18:0) had a great potential in the early diagnosis (both sensitivity and specificity were 100%) and efficacy evaluation (both sensitivity and specificity were 100%) of TB, indicating that the above lipid metabolites could be used as potential biomarkers for TB.

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Section: Discussionsupporting

confidence: 77%

Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients

Chen

Han

Zhang

et al. 2021

Sig Transduct Target Ther

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“…Since excessive inflammation triggers host damage during infection with pathogens, LPC is an attractive target for development of a therapeutic agent. In TB patients, the concentration of LPC in the serum was significantly lower than that in healthy donors ( 43 , 44 ). In addition, Mtb induces macrophage apoptosis through inhibiting phospholipase A 2 , which may offer a reasonable explanation for the lower level of LPC in the serum of TB patients ( 43 ).…”

Section: Discussionmentioning

confidence: 75%

Lysophosphatidylcholine Promotes Phagosome Maturation and Regulates Inflammatory Mediator Production Through the Protein Kinase A–Phosphatidylinositol 3 Kinase–p38 Mitogen-Activated Protein Kinase Signaling Pathway During Mycobacterium tuberculosis Infection in Mouse Macrophages

Lee

Song

et al. 2018

Front. Immunol.

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Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb. In macrophages infected with Mtb strain, H37Ra or H37Rv, LPC suppressed bacterial growth; however, this effect was suppressed in bone marrow-derived macrophages (BMDMs) isolated from G2A (a G protein-coupled receptor involved in some LPC actions) knockout mice. LPC also promoted phagosome maturation via phosphatidylinositol 3 kinase (PI3K)–p38 mitogen-activated protein kinase (MAPK)-mediated reactive oxygen species production and intracellular Ca2+ release during Mtb infection. In addition, LPC induced increased levels of intracellular cyclic adenosine monophosphate (cAMP) and phosphorylated glycogen synthase kinase 3 beta (GSK3β) in Mtb-infected macrophages. Protein kinase A (PKA)-induced phosphorylation of GSK3β suppressed activation of NF-κB in LPC-treated macrophages during Mtb infection, leading to decreased secretion of pro-inflammatory cytokines and increased secretion of anti-inflammatory cytokines. These results suggest that LPC can effectively control Mtb growth by promoting phagosome maturation via cAMP-induced activation of the PKA–PI3K–p38 MAPK pathway. Moreover, LPC can regulate excessive production of pro-inflammatory cytokines associated with bacterial infection of macrophages.

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“…Five glycerophosphocholine species including PC(16:0/18:2), PC(18:0/18:1), PC(18:0/18:2), PC(16:0/16:0) and PC(16:0/18:1) werehigher in bacterial infected samples when compared with viral infected samples. Glycerophosphocholine was elevated in a lipidomics study looking at plasma from tuberculosis patients 44 , however, the exact role of glycerophosphocholine remains elusive. Bilirubin is detected as a consequence of breadth of lipidome coverage, and its role in infection is unclear.…”

Section: Discussionmentioning

confidence: 99%

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Wang

Nijman

Camuzeaux

et al. 2019

Sci Rep

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Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The ‘omics’ approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.

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Plasma Lipidomics of Tuberculosis Patients: Altered Phosphatidylcholine Remodeling

Cited by 9 publications

References 15 publications

Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients

Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients

Lysophosphatidylcholine Promotes Phagosome Maturation and Regulates Inflammatory Mediator Production Through the Protein Kinase A–Phosphatidylinositol 3 Kinase–p38 Mitogen-Activated Protein Kinase Signaling Pathway During Mycobacterium tuberculosis Infection in Mouse Macrophages

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

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