We employ chemical tools, molecular imaging and microbiological techniques to study how bacterial pathogens adapt to environmental conditions, e.g. during infection, and how they respond to antibiotics. We use these insights to develop innovative antimicrobial treatment strategies and chemical probes or sensors for diagnostic applications that are urgently needed in times of emerging drug resistance. More information is found below.
1. Single-cell microbial physiology and biomarker discovery
Antibiotic resistance is, according to the World Health Organization, one of the biggest threats to mankind. Therefore, the development of novel chemotherapeutic and diagnostic strategies for bacterial infections to counter antimicrobial resistance and optimize treatments is an urgent priority requiring a profound understanding of the underlying molecular processes. How bacteria colonize, infect and persist in a host is commonly studied using global read-outs (e.g. genomics, transcriptomics, proteomics) that are performed at the level of entire bacterial populations, providing a phenotypic snapshot of the ‘averaged cell’. That, in fact, single cells or subpopulations of a single bacterial pathogen behave very differently and that this phenotypic heterogeneity contributes to bacterial virulence and problems in clinical management is not commonly taken into account. Two clinically relevant examples for this heterogeneity are e.g. differentiated surface-associated bacterial communities (‘biofilms’) that are difficult to eradicate or ‘persister cell’ subpopulations that are refractory to antibiotic treatment. The sparsity of knowledge on cellular individuality is owed to the simple fact that functionally different cells remain morphologically indistinguishable from each other. Our approach to dissecting bacterial supopulation phenotypes is to use tailored fluorescently tagged small molecule probes as exogenous markers of microbial physiology, and validate their use as biomarkers for different cellular phenotypes. We use a variety of different fluorescent chemical probes, but a focus lies on the use of tailored activity-based probes (ABPs) which are functionalized enzyme inhibitors that covalently bind to the active site of their targets allowing for visualization of their activity. Our long-term goal is to evaluate chemical probes as biomarkers for the development of diagnostic tests to rapidly assess clinically relevant parameters of a bacterial isolate such as metabolic state, antibiotic resistance or virulence.
2. Dissection of bacterial virulence
Bacterial virulence is linked to the remarkable capability of pathogens to survive in different biological niches, such as different tissue sites, biotic and abiotic surfaces and in extracellular and intracellular states. These niches do not only present unique molecular surfaces and nutrient levels, but are also characterized by different stress conditions posed e.g. by the host immune system, microbial competitors, antimicrobial agents and other environmental factors. The corresponding exposure to different molecular environments and the transitioning between niches will require cells to adapt their functional state. In order to identify enzymatic targets that are functionally relevant for bacterial survival, we use chemical proteomics strategies. More specifically, we use functionalized small molecule probes such as activity-based probes to detect, enrich and identify target enzymes. For functional validation of these targets, we will use protein biochemistry and utilize bacterial mutant/reporter strains and chemical probes in different in vitro and in vivo assays.
Are you interested in our research, want to join the team or have more questions? Please do not hesitate do get in touch!
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2004 – 2009 Undergraduate studies (Diploma, equivalent to MSc) in Molecular Biomedicine, University of Bonn, Germany
2009 – 2013 PhD student. Institute of Medical Microbiology, Immunology and Parasitology in collaboration with the Chemical Biology Unit of the Life and Medical Sciences Institute. University of Bonn, Germany. Supervisors: Dr. Kenneth Pfarr, Prof. Achim Hoerauf, Prof. Michael Famulok
2013 - 2014 Postdoctoral fellow at the Institute of Medical Microbiology, University of Bonn, Germany. Supervisors: Dr. Kenneth Pfarr, Prof. Achim Hoerauf
2014 – 2018 Postdoctoral fellow in the research group of Prof. Matthew Bogyo, Department of Pathology, Stanford University, CA, USA
2018 - 2019 Senior postdoc at the Department of Chemical Biology (CBIO), Helmholtz-Centre for Infection Research, Braunschweig, Germany. Head of department: Prof. Mark Broenstrup
Since 2020 Associate professor in Infection Biology, Research Group of Host-Microbe Interactions and Centre for New Antibacterial Strategies (CANS), Department of Medical Biology, Faculty of Health Sciences, UiT – The Arctic University of Norway.
Research and teaching
Publications in peer-reviewed journals
1. Lentz, CS. What you see is what you get: activity-based probes in single-cell analysis of enzymatic activities. Biol Chem. 2020 Feb 25;401(2):233-248. Review article
2. Chen L., Keller LJ, Cordasco E, Bogyo M#, Lentz CS#. Single-cell phenotypic characterization of Staphylococcus aureus with fluorescent triazole urea activity-based probes. Angew. Chem. Int. Ed. (2019). 58(17):5643-5647. # Corresponding author(s)
3. Manna D, Lentz CS, Ehrenkaufer G, Suresh S., Bhat A, Singh U. An NAD+ dependent novel transcription factor controls stage conversion in Entamoeba. eLife (2018) Oct 30;7. pii: e37912. doi: 10.7554/eLife.37912.
4. Lentz CS*, Sheldon JR*, Crawford L, Cooper R, Garland M, Weerapana E, Amieva M, Skaar EP, Bogyo M. Identification of a Staphylococcus aureus virulence factor by activity-based protein profiling (ABPP). Nature Chem. Biol. (2018) 14, 609–617. DOI:10.1038/s41589-018-0060-1.
*CSL and JRS contributed equally to this work.
5. Tomlin FM, Gerling-Driessen UIM, Liu Y-C, Flynn, RA, Vangala JR, Lentz CS, Clauder-Muenster S, Jakob P, Mueller WF, Ordonez-Rueda D, Paulsen M, Matsui N, Foley D, Rafalko A, Shirakura T, Suzuki T, Bogyo M, Steinmetz LM, Radhakrishnan SK, Bertozzi CR. Inhibition of NGLY1 inactivates the transcription factor Nrf1 and potentiates proteasome inhibitor cytotoxicity. ACS Cent. Sci. (2017) 3(11):1143-1155. DOI: 10.1021/acscentsci.7b00224.
6. Lentz CS, Ordonez AA Kasperkiewicz P, La Greca F, O'Donoghue A, Schulze, CJ, Powers JC, Craik CS, Drag M, Jain SK, Bogyo M. Design of selective substrates and activity-based probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis. ACS Infect Dis. (2016) 2(11):807-815.
7. Lentz CS, Sattler JM, Fendler M, Gottwald S, Halls VS, Strassel S, Arriens S, Hannam JS, Specht S, Famulok M, Mueller AK, Hoerauf A, Pfarr KM. In vitro activity of wALADin benzimidazoles against different life cycle stages of Plasmodium parasites. Antimicrob Agents Chemother (2015) 59(1):654-8.
8. Lentz CS, Halls VS, Hannam JS, Strassel S, Lawrence SH, Jaffe EK, Famulok M, Hoerauf A, Pfarr KM. wALADin benzimidazoles differentially modulate the function of porphobilinogen synthase orthologs. J Med Chem. (2014) 57(6):2498-510.
9. Gentil K*, Lentz CS*, Rai R, Muhsin M, Kamath AD, Mutluer O, Specht S, Huebner MP, Hoerauf A. Eotaxin-1 is required for parasite clearance during chronic filarial infection. Parasite Immunol (2014) 36(2):60-77.
*KG and CSL contributed equally to this work.
10. Schiefer A, Vollmer J, Laemmer C, Specht S, Lentz C, Ruebsamen-Schaeff H, Broetz-Oesterhelt H, Hoerauf A, Pfarr K. The ClpP peptidase of Wolbachia endobacteria is a novel target for drug development against filarial infections. J Antimicrob Chemother (2013) 68(8):1790-800.
11. Lentz CS, Stumpfe D, Bajorath J, Famulok M, Hoerauf A, Pfarr KM. New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria. Bioorg Med Chem Lett (2013) 23(20):5558-62.
12. Lentz CS*, Halls V*, Hannam JS, Niebel B, Struebing U, Mayer G, Hoerauf A, Famulok M., Pfarr KM. A selective inhibitor of heme biosynthesis in endosymbiotic bacteria elicits antifilarial activity in vitro. Cell Chem Biol (2013) 21;20(2): 177-87.
*CSL and VH contributed equally to this work.
13. Niebel B, Lentz C, Pofahl M, Mayer G, Hoerauf A, Pfarr KM, Famulok M. ADLOC: an aptamer displacement assay based on luminescent oxygen channeling. Chemistry (2010) 16(36): 11100-7.