Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems (2023)

Abstract

The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix-assisted laser desorption-ionization-coupled applications. NRM matrix improved the limit of detection (LOD) for monophosphoryl lipid A (MPLA) down to picogram level representing a 10-fold improvement of LOD versus 2,5-dihydroxybenzoic acid and 100-fold improvement of LOD versus 9-aminoacridine (9-AA). Improved LOD for lipid A subsequently facilitated detection of the Fn lipid A major ion (m/z 1665) from extracts of infected mouse spleen and the temperature-modified Fn lipid A at m/z 1637 from infected Dermacentor variabilis ticks. Finally, we simultaneously mapped bacterial phospholipid signatures within an Fn-infected spleen along with an exclusively host-derived inositol-based phospholipid (m/z 933) demonstrating coprofiling of the host-pathogen interaction. Expanded use of NRM matrix in other infection models and endotoxin-targeting imaging experiments will improve our understanding of the lipid interactions at the host-pathogen interface.

Original languageEnglish
Article numberftw097
JournalPathogens and Disease
Volume74
Issue number8
DOIs
Publication statusPublished - Nov 2016

Keywords

  • mass spectrometry imaging
  • host-pathogen interaction
  • endotoxin

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Scott, A. J., Flinders, B., Cappell, J., Liang, T., Pelc, R. S., Tran, B., Kilgour, D. P. A., Heeren, R. M. A., Goodlett, D. R., & Ernst, R. K. (2016). Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems. Pathogens and Disease, 74(8), [ftw097]. https://doi.org/10.1093/femspd/ftw097

Scott, Alison J. ; Flinders, Bryn ; Cappell, Jo et al. / Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems. In: Pathogens and Disease. 2016 ; Vol. 74, No. 8.

@article{08793939d0a5406f9e257443eea00758,

title = "Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems",

abstract = "The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix-assisted laser desorption-ionization-coupled applications. NRM matrix improved the limit of detection (LOD) for monophosphoryl lipid A (MPLA) down to picogram level representing a 10-fold improvement of LOD versus 2,5-dihydroxybenzoic acid and 100-fold improvement of LOD versus 9-aminoacridine (9-AA). Improved LOD for lipid A subsequently facilitated detection of the Fn lipid A major ion (m/z 1665) from extracts of infected mouse spleen and the temperature-modified Fn lipid A at m/z 1637 from infected Dermacentor variabilis ticks. Finally, we simultaneously mapped bacterial phospholipid signatures within an Fn-infected spleen along with an exclusively host-derived inositol-based phospholipid (m/z 933) demonstrating coprofiling of the host-pathogen interaction. Expanded use of NRM matrix in other infection models and endotoxin-targeting imaging experiments will improve our understanding of the lipid interactions at the host-pathogen interface.",

keywords = "mass spectrometry imaging, host-pathogen interaction, endotoxin",

author = "Scott, {Alison J.} and Bryn Flinders and Jo Cappell and Tao Liang and Pelc, {Rebecca S.} and Bao Tran and Kilgour, {David P. A.} and Heeren, {Ron M. A.} and Goodlett, {David R.} and Ernst, {Robert K.}",

year = "2016",

month = nov,

doi = "10.1093/femspd/ftw097",

language = "English",

volume = "74",

journal = "Pathogens and Disease",

issn = "2049-632X",

publisher = "Oxford University Press",

number = "8",

}

Scott, AJ, Flinders, B, Cappell, J, Liang, T, Pelc, RS, Tran, B, Kilgour, DPA, Heeren, RMA, Goodlett, DR & Ernst, RK 2016, 'Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems', Pathogens and Disease, vol. 74, no. 8, ftw097. https://doi.org/10.1093/femspd/ftw097

Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems. / Scott, Alison J.; Flinders, Bryn; Cappell, Jo et al.

In: Pathogens and Disease, Vol. 74, No. 8, ftw097, 11.2016.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems

AU - Scott, Alison J.

AU - Flinders, Bryn

AU - Cappell, Jo

AU - Liang, Tao

AU - Pelc, Rebecca S.

AU - Tran, Bao

AU - Kilgour, David P. A.

AU - Heeren, Ron M. A.

AU - Goodlett, David R.

AU - Ernst, Robert K.

PY - 2016/11

Y1 - 2016/11

N2 - The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix-assisted laser desorption-ionization-coupled applications. NRM matrix improved the limit of detection (LOD) for monophosphoryl lipid A (MPLA) down to picogram level representing a 10-fold improvement of LOD versus 2,5-dihydroxybenzoic acid and 100-fold improvement of LOD versus 9-aminoacridine (9-AA). Improved LOD for lipid A subsequently facilitated detection of the Fn lipid A major ion (m/z 1665) from extracts of infected mouse spleen and the temperature-modified Fn lipid A at m/z 1637 from infected Dermacentor variabilis ticks. Finally, we simultaneously mapped bacterial phospholipid signatures within an Fn-infected spleen along with an exclusively host-derived inositol-based phospholipid (m/z 933) demonstrating coprofiling of the host-pathogen interaction. Expanded use of NRM matrix in other infection models and endotoxin-targeting imaging experiments will improve our understanding of the lipid interactions at the host-pathogen interface.

AB - The discovery of novel pathogenic mechanisms engaged during bacterial infections requires the evolution of advanced techniques. Here, we evaluate the dual polarity matrix norharmane (NRM) to improve detection of bacterial lipid A (endotoxin), from host and vector tissues infected with Francisella novicida (Fn). We evaluated NRM for improved detection and characterization of a wide range of lipids in both positive and negative polarities, including lipid A and phospholipids across a range of matrix-assisted laser desorption-ionization-coupled applications. NRM matrix improved the limit of detection (LOD) for monophosphoryl lipid A (MPLA) down to picogram level representing a 10-fold improvement of LOD versus 2,5-dihydroxybenzoic acid and 100-fold improvement of LOD versus 9-aminoacridine (9-AA). Improved LOD for lipid A subsequently facilitated detection of the Fn lipid A major ion (m/z 1665) from extracts of infected mouse spleen and the temperature-modified Fn lipid A at m/z 1637 from infected Dermacentor variabilis ticks. Finally, we simultaneously mapped bacterial phospholipid signatures within an Fn-infected spleen along with an exclusively host-derived inositol-based phospholipid (m/z 933) demonstrating coprofiling of the host-pathogen interaction. Expanded use of NRM matrix in other infection models and endotoxin-targeting imaging experiments will improve our understanding of the lipid interactions at the host-pathogen interface.

KW - mass spectrometry imaging

KW - host-pathogen interaction

KW - endotoxin

U2 - 10.1093/femspd/ftw097

DO - 10.1093/femspd/ftw097

M3 - Article

C2 - 27650574

SN - 2049-632X

VL - 74

JO - Pathogens and Disease

JF - Pathogens and Disease

IS - 8

M1 - ftw097

ER -

Scott AJ, Flinders B, Cappell J, Liang T, Pelc RS, Tran B et al. Norharmane matrix enhances detection of endotoxin by MALDI-MS for simultaneous profiling of pathogen, host and vector systems. Pathogens and Disease. 2016 Nov;74(8):ftw097. doi: 10.1093/femspd/ftw097

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