Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens
Bacteremia—i.e., the presence of pathogens in the blood stream—is associated with long-term morbidity and is a potential precursor condition to life-threatening sepsis. Timely detection of bacteremia is therefore critical to reduce patient mortality, but existing methods lack precision, speed, and s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/3/516 |
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| author | Sayantani Chatterjee Rebeca Kawahara Harry C. Tjondro David R. Shaw Marni A. Nenke David J. Torpy Morten Thaysen-Andersen |
| author_facet | Sayantani Chatterjee Rebeca Kawahara Harry C. Tjondro David R. Shaw Marni A. Nenke David J. Torpy Morten Thaysen-Andersen |
| author_sort | Sayantani Chatterjee |
| collection | DOAJ |
| description | Bacteremia—i.e., the presence of pathogens in the blood stream—is associated with long-term morbidity and is a potential precursor condition to life-threatening sepsis. Timely detection of bacteremia is therefore critical to reduce patient mortality, but existing methods lack precision, speed, and sensitivity to effectively stratify bacteremic patients. Herein, we tested the potential of quantitative serum <i>N</i>-glycomics performed using porous graphitized carbon liquid chromatography tandem mass spectrometry to stratify bacteremic patients infected with <i>Escherichia coli</i> (<i>n</i> = 11), <i>Staphylococcus aureus</i> (<i>n</i> = 11), <i>Pseudomonas aeruginosa</i> (<i>n</i> = 5), and <i>Streptococcus viridans</i> (<i>n</i> = 5) from healthy donors (<i>n</i> = 39). In total, 62 <i>N</i>-glycan isomers spanning 41 glycan compositions primarily comprising complex-type core fucosylated, bisecting <i>N</i>-acetylglucosamine (GlcNAc), and α2,3-/α2,6-sialylated structures were profiled across all samples using label-free quantitation. Excitingly, unsupervised hierarchical clustering and principal component analysis of the serum <i>N</i>-glycome data accurately separated the patient groups. <i>P. aeruginosa</i>-infected patients displayed prominent <i>N</i>-glycome aberrations involving elevated levels of fucosylation and bisecting GlcNAcylation and reduced sialylation relative to other bacteremic patients. Notably, receiver operating characteristic analyses demonstrated that a single <i>N</i>-glycan isomer could effectively stratify each of the four bacteremic patient groups from the healthy donors (area under the curve 0.93–1.00). Thus, the serum <i>N</i>-glycome represents a new hitherto unexplored class of potential diagnostic markers for bloodstream infections. |
| first_indexed | 2024-03-09T06:12:25Z |
| format | Article |
| id | doaj.art-3037aec27d934c3792597d5a65dcd1f5 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T06:12:25Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-3037aec27d934c3792597d5a65dcd1f52023-12-03T11:56:48ZengMDPI AGJournal of Clinical Medicine2077-03832021-02-0110351610.3390/jcm10030516Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different PathogensSayantani Chatterjee0Rebeca Kawahara1Harry C. Tjondro2David R. Shaw3Marni A. Nenke4David J. Torpy5Morten Thaysen-Andersen6Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, AustraliaDepartment of Molecular Sciences, Macquarie University, Sydney, NSW 2109, AustraliaDepartment of Molecular Sciences, Macquarie University, Sydney, NSW 2109, AustraliaInfectious Diseases Clinic, Royal Adelaide Hospital, Adelaide, SA 5000, AustraliaEndocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, AustraliaEndocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, AustraliaDepartment of Molecular Sciences, Macquarie University, Sydney, NSW 2109, AustraliaBacteremia—i.e., the presence of pathogens in the blood stream—is associated with long-term morbidity and is a potential precursor condition to life-threatening sepsis. Timely detection of bacteremia is therefore critical to reduce patient mortality, but existing methods lack precision, speed, and sensitivity to effectively stratify bacteremic patients. Herein, we tested the potential of quantitative serum <i>N</i>-glycomics performed using porous graphitized carbon liquid chromatography tandem mass spectrometry to stratify bacteremic patients infected with <i>Escherichia coli</i> (<i>n</i> = 11), <i>Staphylococcus aureus</i> (<i>n</i> = 11), <i>Pseudomonas aeruginosa</i> (<i>n</i> = 5), and <i>Streptococcus viridans</i> (<i>n</i> = 5) from healthy donors (<i>n</i> = 39). In total, 62 <i>N</i>-glycan isomers spanning 41 glycan compositions primarily comprising complex-type core fucosylated, bisecting <i>N</i>-acetylglucosamine (GlcNAc), and α2,3-/α2,6-sialylated structures were profiled across all samples using label-free quantitation. Excitingly, unsupervised hierarchical clustering and principal component analysis of the serum <i>N</i>-glycome data accurately separated the patient groups. <i>P. aeruginosa</i>-infected patients displayed prominent <i>N</i>-glycome aberrations involving elevated levels of fucosylation and bisecting GlcNAcylation and reduced sialylation relative to other bacteremic patients. Notably, receiver operating characteristic analyses demonstrated that a single <i>N</i>-glycan isomer could effectively stratify each of the four bacteremic patient groups from the healthy donors (area under the curve 0.93–1.00). Thus, the serum <i>N</i>-glycome represents a new hitherto unexplored class of potential diagnostic markers for bloodstream infections.https://www.mdpi.com/2077-0383/10/3/516bacteremiabiomarkermass spectrometry<i>N</i>-glycan<i>N</i>-glycomicsporous graphitized carbon |
| spellingShingle | Sayantani Chatterjee Rebeca Kawahara Harry C. Tjondro David R. Shaw Marni A. Nenke David J. Torpy Morten Thaysen-Andersen Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens Journal of Clinical Medicine bacteremia biomarker mass spectrometry <i>N</i>-glycan <i>N</i>-glycomics porous graphitized carbon |
| title | Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens |
| title_full | Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens |
| title_fullStr | Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens |
| title_full_unstemmed | Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens |
| title_short | Serum <i>N</i>-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens |
| title_sort | serum i n i glycomics stratifies bacteremic patients infected with different pathogens |
| topic | bacteremia biomarker mass spectrometry <i>N</i>-glycan <i>N</i>-glycomics porous graphitized carbon |
| url | https://www.mdpi.com/2077-0383/10/3/516 |
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