Lea Mann
Lea Mann
Within the inhomogeneous family of non-tuberculous mycobacteria (NTMs), Mycobacterium avium complex (MAC) and Mycobacterium abscessus are the most common pathogens associated with non-tuberculosis lung disease. It should be emphasized that pulmonary infections with Mycobacterium abscessus, in particular, are extremely difficult to treat due to high intrinsic drug resistance and adaptability to different habitats, so that infections with Mycobacterium abscessus are often referred as an "incurable nightmare."
In order to characterize potential drug candidates against mycobacteria, appropriate testing methods are required.
My research is focussed on the in vitro evaluation of compounds against various NTMs, such as Mycobacterium abscessus, Mycobacterium aurum and Mycobacterium smegmatis, with great emphasis on the predictivity of the methods for in vivo infection.
Three or more antibiotics are usually used to treat an infection with Mycobacterium abscessus. A "checkerboard" assay allows to investigate two antiinfective agents in up to eighty different concentration combinations on a 96-well plate and enables predictions about the synergy of antibiotics.
Since Mycobacterium abscessus, like Mycobacterium avium, has the ability to persist and replicate within macrophages, working with models that represent the infection in human macrophages is an important part of my work. A fluorescence-based high-throughput assay was developed that allows efficient testing of drug candidates during macrophage infection.
Overall, assays will be established to realize the efficient and valid testing of drug candidates and to optimize them regarding the characteristics of NTMs.
List of publications
Mann L, Ganapathy US, Abdelaziz R, Lang M, Zimmerman MD, Dartois V, Dick T, Richter A. 2022. In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus. Microbiol Spectr https://doi.org/10.1128/SPECTRUM.02760-22.
Richter A, Seidel RW, Goddard R, Eckhardt T, Lehmann C, Dörner J, Siersleben F, Sondermann T, Mann L, Patzer M, Jäger C, Reiling N, Imming P. 2022. BTZ-Derived Benzisothiazolinones with In Vitro Activity against Mycobacterium tuberculosis. ACS Med Chem Lett https://doi.org/10.1021/acsmedchemlett.2c00215.
Beuchel A, Robaa D, Negatu DA, Madani A, Alvarez N, Zimmerman MD, Richter A, Mann L, Hoenke S, Csuk R, Dick T, Imming P. 2022. Structure-Activity Relationship of Anti-Mycobacterium abscessus Piperidine-4-carboxamides, a New Class of NBTI DNA Gyrase Inhibitors. ACS Med Chem Lett 13:417–427.
Sirak B, Mann L, Richter A, Asres K, Imming P. 2021. In vivo antimalarial activity of leaf extracts and a major compound isolated from ranunculus multifidus forsk. Molecules 26:1–16.
Mann L, Lang M, Schulze P, Halz JH, Csuk R, Hoenke S, Seidel RW, Richter A. 2021. Racemization-free synthesis of Nα-2-thiophenoyl-phenylalanine-2-morpholinoanilide enantiomers and their antimycobacterial activity. Amino Acids 53:1187–1196.