Dr. Adrian Richter
photo: Dr. Adrian Richter
May 2020;
source: private
The aim of the research project is the development and characterization of substances with activity against non-tuberculous mycobacteria. These germs, e.g. Mycobacterium abscessus, avium and intracellulare are often referred as "incurable nightmare", because of high level resistance against antibiotics.
In most cases, patients with a suppressed immune status or a structural lung disease, for example cystic fibrosis, are affected. Non-tuberculous mycobacteria cause lung tissue infections, but those bacteria can also affect the skin and central nervous system. The treatment of these infections is currently insufficient, because of the lack of effective antibiotics.
The research project will be implemented by an interdisciplinary use of methods of medical chemistry and microbiology and aimed at the development of a drug candidate that combines high activity against non-tuberculous mycobacteria with good pharmacokinetic properties. The starting point of the project is to investigate drug targets, which are already established against Mycobacterium tuberculosis, for the treatment of non-tuberculous mycobacteria. For this purpose inhibitors for the mycobacterial enzymes ATP-synthase, DprE1 and RNA-polymerase are to be synthesized, tested and optimized against the above-mentioned bacteria.
An important component is the development of microbiological assays for various mycobacterial species, such as Mycobacterium abscessus and avium, which reflect the conditions during infection in the human body better than conventional in vitro methods. Since the bacteria have the ability to infect human macrophages, an assay is to be established that simulates these conditions well. The development of this macrophage infection assay allows the investigation of substances that inhibit bacterial growth by acting on the host cell ("host directed therapy").
The main goals of the project are a better understanding of the mechanisms of action/resistance in non-tuberculous mycobacteria and the development of a lead compound suitable for preclinical characterization.
Professional CV
since 2nd June 2019 scientific associate at Martin-Luther-University Halle-Wittenberg
2nd June 2017 to 1st June 2019 post-doc at the research group of Prof. Yossef Av-Gay at the University of British Columbia (Targeting intracellular Mycobacterium abscessus and Mycobacterium tuberculosis for drug discovery)
27th March 2017 defence of the dissertation „Synthese von Benzothiazinonen und Derivaten als DprE1 Hemmstoffe mit antimykobakterieller Aktivität“ (Synthesis of benzothiazinones and derivates as DprE1-inhibitors, summa cum laude) awarded the research prize Bayer Bitterfeld GmbH 2016/17
1st January 2017 to 31st May 2017 pharmacist at Apotheke Zur Goldenen Aue Roßleben
1st January 2013 to 31st December 2016 doctoral candidate at the research group of Prof. Peter Imming, Martin-Luther-University Halle-Wittenberg
01st May 2012 to 31st December 2013 practical training as a pharmacist at the Löwen-Apotheke Naumburg/Saale and the Apotheke Zur Goldenen Aue Roßleben - (licence as a pharmacist)
1st November 2011 to 30th April 2012 diploma student at the research group of Prof. Peter Imming, Martin-Luther-University Halle-Wittenberg (Synthesis of structural modifications of the natural substance pyridomycine)
2007 to 2011 studies of Pharmacy at the Martin-Luther-University Halle-Wittenberg
Research visits
23th November 2015 to 7th December 2015 King´s College London, Development of formulation strategies of benzothiazinones, mentor: Dr. Lea Ann Dailey
6th May 2014 to 7th May 2014 Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) Jena, anti(myco)bacterial assays of benzothiazinone derivates, mentor: Christiane Weigel
15th June 2013 to 29th June 2013 GSK R&D Stevenage, assays of benzothiazinones in DprE1 enzyme assays, DprE1 co-crystallisation experiments, mentor: Dr. Onkar Singh, Dr. Argyrides Argyrou
Teaching experience
Supervision of students in the practical course "Chemie organischer Arznei-, Gift- und Hilfsstoffe" (Chemistry of organic drug substances, toxins and pharmaceutical auxiliaries)
Supervision of advanced students and diploma students during work at the research group of Prof. Dr. Imming
List of publications
Richter A, Shapira T, Av-Gay Y. THP-1 and Dictyostelium infection models for screening and characterization of anti-Mycobacterium abscessus hit compounds. Antimicrobial Agents and Chemotherapy 2019, AAC.01601-19; DOI: 10.1128/AAC.01601-19
Richter A, Strauch A, Chao J, Ko M, Av-Gay Y. Screening of Preselected Libraries Targeting Mycobacterium abscessus for Drug Discovery. Antimicrobial Agents and Chemotherapy 2018, 62 (9) e00828-18; DOI: 10.1128/AAC.00828-18
Richter A, Rudolph I, Möllmann U, Voigt K, Chung CW, Singh OMP, Rees M, Mendoza-Losana A, Bates R, Ballell L, Batt S, Veerapen N, Fütterer K, Besra G, Imming P, Argyrou A. Novel in-sight into the reaction of nitro, nitroso and hydroxylamino benzothiazinones and of benzoxacinones with Mycobacterium tuberculosis DprE1. Sci Rep. 2018 8:13473.
Laqua K, Klemm M, Richard-Greenblatt M, Richter A, Liebe L, Huang T, Lin S, Guardia A, Pérez-Herran E, Ballell L, Av-Gay Y, Imming P. Synthesis, antimycobacterial activity and influence on mycobacterial InhA and PknB of 12-membered cyclodepsipeptides. Bioorg Med Chem. 2018 26:3166-3190.
Deusche Forschungsgemeinschaft;
source: DFG
The Deutsche Forschungsgemeinschaft (German research community) supports the poject "Development of drug candidates with activity against Mycobacterium abscessus and different non-tuberculous mycobacteria - Synthesis, Assay Development and Microbiological Characterisation"