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. 2016 Feb 27;17(3):307.
doi: 10.3390/ijms17030307.

Metabolomic Profiling of Plasma From Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

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Free PMC article

Metabolomic Profiling of Plasma From Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

Susanna K P Lau et al. Int J Mol Sci. .
Free PMC article

Abstract

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

Keywords: Burkholderia pseudomallei; biomarkers; melioidosis; metabolomics; plasma.

Figures

Figure 1
Figure 1
Principal component analysis (PCA) score plot in positive mode based on human plasma of 22 melioidosis, 24 bacteremia and 30 controls without active infection. The PCA score plots showed that samples from melioidosis patients, bacteremia patients and controls without active infection were clustered separately.
Figure 2
Figure 2
Volcano Plot, using fold-change (FC) >1.5 and p-values cut-off <0.05 using Student’s t-test. The statistical analyses were performed for comparison between melioidosis and bacteremia patients in (A) positive mode as well as melioidosis patients and controls without active infection in (B) positive mode.
Figure 3
Figure 3
MS/MS mass spectra and predicted structures with expected fragmentation profiles of the 12 biomarkers in melioidosis patient plasma: (A) l-octanoylcarnitine; (B) decanoylcarnitine; (C) dodecanoylcarnitine; (D) lysophosphatidylethanolamine (LysoPE)(16:0/0:0); (E) LysoPE(18:0/0:0); (F) phosphatidylcholine PC(16:0/16:0); (G) LysoPE(0:0/18:0) (H) l-hexanoylcarnitine; (I) sphingomyelins SM(d16:1/16:0); (J) 2-decenoylcarnitine; (K) SM(d18:2/16:0); and (L) trans-2-dodecenoylcarnitine with or without comparison to commercially available standards.
Figure 3
Figure 3
MS/MS mass spectra and predicted structures with expected fragmentation profiles of the 12 biomarkers in melioidosis patient plasma: (A) l-octanoylcarnitine; (B) decanoylcarnitine; (C) dodecanoylcarnitine; (D) lysophosphatidylethanolamine (LysoPE)(16:0/0:0); (E) LysoPE(18:0/0:0); (F) phosphatidylcholine PC(16:0/16:0); (G) LysoPE(0:0/18:0) (H) l-hexanoylcarnitine; (I) sphingomyelins SM(d16:1/16:0); (J) 2-decenoylcarnitine; (K) SM(d18:2/16:0); and (L) trans-2-dodecenoylcarnitine with or without comparison to commercially available standards.
Figure 3
Figure 3
MS/MS mass spectra and predicted structures with expected fragmentation profiles of the 12 biomarkers in melioidosis patient plasma: (A) l-octanoylcarnitine; (B) decanoylcarnitine; (C) dodecanoylcarnitine; (D) lysophosphatidylethanolamine (LysoPE)(16:0/0:0); (E) LysoPE(18:0/0:0); (F) phosphatidylcholine PC(16:0/16:0); (G) LysoPE(0:0/18:0) (H) l-hexanoylcarnitine; (I) sphingomyelins SM(d16:1/16:0); (J) 2-decenoylcarnitine; (K) SM(d18:2/16:0); and (L) trans-2-dodecenoylcarnitine with or without comparison to commercially available standards.
Figure 3
Figure 3
MS/MS mass spectra and predicted structures with expected fragmentation profiles of the 12 biomarkers in melioidosis patient plasma: (A) l-octanoylcarnitine; (B) decanoylcarnitine; (C) dodecanoylcarnitine; (D) lysophosphatidylethanolamine (LysoPE)(16:0/0:0); (E) LysoPE(18:0/0:0); (F) phosphatidylcholine PC(16:0/16:0); (G) LysoPE(0:0/18:0) (H) l-hexanoylcarnitine; (I) sphingomyelins SM(d16:1/16:0); (J) 2-decenoylcarnitine; (K) SM(d18:2/16:0); and (L) trans-2-dodecenoylcarnitine with or without comparison to commercially available standards.
Figure 3
Figure 3
MS/MS mass spectra and predicted structures with expected fragmentation profiles of the 12 biomarkers in melioidosis patient plasma: (A) l-octanoylcarnitine; (B) decanoylcarnitine; (C) dodecanoylcarnitine; (D) lysophosphatidylethanolamine (LysoPE)(16:0/0:0); (E) LysoPE(18:0/0:0); (F) phosphatidylcholine PC(16:0/16:0); (G) LysoPE(0:0/18:0) (H) l-hexanoylcarnitine; (I) sphingomyelins SM(d16:1/16:0); (J) 2-decenoylcarnitine; (K) SM(d18:2/16:0); and (L) trans-2-dodecenoylcarnitine with or without comparison to commercially available standards.
Figure 4
Figure 4
Box-and-whiskers plots representing relative abundance of: (A) l-hexanoylcarnitine; (B) l-octanoylcarnitine; (C) 2-decenoylcarnitine; (D) decanoylcarnitine; (E) trans-2-dodecenoylcarnitine; (F) dodecanoylcarnitine; (G) LysoPE(16:0/0:0); (H) LysoPE(0:0/18:0); (I) LysoPE(18:0/0:0); (J) SM(d16:1/16:0); (K) SM(d18:2/16:0); and (L) PC(16:0/16:0) in plasma of melioidosis patients, bacteremia patients and controls without active infections. The relative abundance of each metabolite in plasma of melioidosis patients was significantly higher than the other two groups using Student’s t-test (p-value < 0.01).
Figure 5
Figure 5
Receiver operating characteristic (ROC) curves for SM(d18:2/16:0) with Area Under the Curves (AUC) with 95% confidence interval, when compared (A) between melioidosis and other bacteremia patients; and (B) between melioidosis patients and controls without active infection.

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References

    1. Anuradha K., Meena A.K., Lakshmi V. Isolation of Burkholderia pseudomallei from a case of septicaemia—A case report. Indian J. Med. Microbiol. 2003;21:129–132. - PubMed
    1. Saravu K., Mukhopadhyay C., Vishwanath S., Valsalan R., Docherla M., Vandana K.E., Shastry B.A., Bairy I., Rao S.P. Melioidosis in southern India: Epidemiological and clinical profile. Southeast. Asian J. Trop. Med. Public Health. 2010;41:401–409. - PubMed
    1. Issack M.I., Bundhun C.D., Gokhool H. Melioidosis in Mauritius. Emerg. Infect. Dis. 2005;11:139–140. doi: 10.3201/eid1101.040605. - DOI - PMC - PubMed
    1. Inglis T.J., Rolim D.B., Sousa Ade Q. Melioidosis in the Americas. Am. J. Trop Med. Hyg. 2006;75:947–954. - PubMed
    1. Rolim D.B., Vilar D.C., Sousa A.Q., Miralles I.S., de Oliveira D.C., Harnett G., O’Reilly L., Howard K., Sampson I., Inglis T.J. Melioidosis, northeastern Brazil. Emerg. Infect. Dis. 2005;11:1458–1460. doi: 10.3201/eid1109.050493. - DOI - PMC - PubMed

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