Czech Society for Mass Spectrometry

(Czech Mass Spectrometry Conference 2019 - PL-02)
Lipid A as a Therapeutic and Diagnostic

David Goodlett ^1 *

1. University of Maryland, Baltimore

Abstract

Lipid A is the membrane anchor for Gram-negative bacteria that holds the much larger lipopolysaccharide (LPS) molecule in place in the outer membrane. Importantly in mammals, Toll-like receptor 4 (TLR4) recognizes lipid A the result of which is activation of a cytokine cascade that can aid the host in clearing the infection or if unchecked lead to a deadly cytokine storm. There are a range of activities from agonistic to antagonistic that are directly related to structure (e.g. Li). To exploit this we are working to better define the lipid A structure activity relationship for use as a vaccine adjuvants and antisepsis therapeutics (e.g. Scott, [1]). We are also using lipid A and related Gram-positive molecules to identify bacteria direct from source in under an hour (Leung, [2]). At the ICCVS in Gdansk we are interested in investigating the classic use of bacterial extracts as an immunotherapy (i.e. Coley’s toxins late 1800s NYC) that have been recently revived (Kim, [3]). We are also working to define protein antigens that can be used as imaging agents, therapeutics and diagnostics in point of care devices (Freiberg, [3]). I’ll present the above topics from the perspective of how mass spectrometry is helping to solve these problems.

* Corresponding author: david.goodlett@gmail.com

References

1. Scott A.J. et al.: BBA Mol. Cell. Biol. Lipids 1862, 1439-1450 (2017).
2. Yoon S.H. et al.: Rapid Commun. Mass Spectrom. 30, 2555-2560 (2016); Leung L.M. et al.: Sci. Rep. 7, 6403 (2017).
3. Freiberg J.A. et al.: mSystems 1, e00149-16 (2016); Kim O.Y. et al.: Nat. Commun. 8, 626 (2017).