High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types

Landry Blanc, Isaac B. Daudelin, Brendan K. Podell, Pei Yu Chen, Matthew Zimmerman, Amanda J. Martinot, Rada M. Savic, Brendan Prideaux, Véronique Dartois

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Understanding the distribution patterns of antibiotics at the site of infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made of various immune cell types, some of which harbor persistent forms of the pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining and quantitative image analysis in rabbits with active TB, we have mapped the distribution of a fluoroquinolone at high resolution, and identified the immune-pathological factors driving its heterogeneous penetration within TB lesions, in relation to where bacteria reside. We find that macrophage content, distance from lesion border and extent of necrosis drive the uneven fluoroquinolone penetration. Preferential uptake in macrophages and foamy macrophages, where persistent bacilli reside, compared to other immune cells present in TB granulomas, was recapitulated in vitro using primary human cells. A nonlinear modeling approach was developed to help predict the observed drug behavior in TB lesions. This work constitutes a methodological advance for the co-localization of drugs and infectious agents at high spatial resolution in diseased tissues, which can be applied to other diseases with complex immunopathology.

Original languageEnglish (US)
Article numbere41115
JournaleLife
Volume7
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

Fingerprint

Macrophages
Fluoroquinolones
Tuberculosis
Rabbits
Pharmaceutical Preparations
Anti-Bacterial Agents
Histology
Immunologic Factors
Pathogens
Bacilli
Ports and harbors
Image analysis
Bacteria
Cells
Tissue
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Granuloma
Mycobacterium tuberculosis
Bacillus
Necrosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Blanc, L., Daudelin, I. B., Podell, B. K., Chen, P. Y., Zimmerman, M., Martinot, A. J., ... Dartois, V. (2018). High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types. eLife, 7, [e41115]. https://doi.org/10.7554/eLife.41115

High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types. / Blanc, Landry; Daudelin, Isaac B.; Podell, Brendan K.; Chen, Pei Yu; Zimmerman, Matthew; Martinot, Amanda J.; Savic, Rada M.; Prideaux, Brendan; Dartois, Véronique.

In: eLife, Vol. 7, e41115, 01.11.2018.

Research output: Contribution to journalArticle

Blanc, L, Daudelin, IB, Podell, BK, Chen, PY, Zimmerman, M, Martinot, AJ, Savic, RM, Prideaux, B & Dartois, V 2018, 'High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types', eLife, vol. 7, e41115. https://doi.org/10.7554/eLife.41115
Blanc, Landry ; Daudelin, Isaac B. ; Podell, Brendan K. ; Chen, Pei Yu ; Zimmerman, Matthew ; Martinot, Amanda J. ; Savic, Rada M. ; Prideaux, Brendan ; Dartois, Véronique. / High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types. In: eLife. 2018 ; Vol. 7.
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