Interfaculty Institute of Microbiology and Infection Medicine



Research articles / Reviews (Heike Brötz-Oesterhelt)

2015 to date

Schilling NA, Berscheid A, Schumacher J, Saur JS, Konnerth MC, Wirtz SN, Beltrán Beleña JM, Zipperer A, Krismer B, Peschel A, Kalbacher H, Brötz-Oesterhelt H, Steinem C, Grond SC. 2019. Synthetic lugdunin analogues reveal essential structural motifs for antimicrobial action and proton translocation capability. Angew Chem Int Ed Engl. 2019 May 6. doi: 10.1002/anie.201901589. [Epub ahead of print]. 

Lennings J, Mayer C, Makhlouf M, Brötz-Oesterhelt H, Schwarz S. 2019. Polar localization of the ATPase ClpV-5 occurs independent of type VI secretion system apparatus proteins in Burkholderia thailandensis. BMC Res Notes. 2019 Feb 28;12(1):109. doi: 10.1186/s13104-019-4141-3. 

Moreno-Cinos C, Sassetti E, Salado IG, Witt G, Benramdane S, Reinhardt L, Durante Cruz C, Joossens J, Van der Veken P, Brotz-Oesterhelt H, Tammela P, Winterhalter M, Gribbon P, Windshügel B, Augustyns K. 2018. α-Amino diphenyl phosphonates as novel inhibitors of Escherichia coli ClpP protease. J Med Chem. 2018 Dec 20. doi: 10.1021/acs.jmedchem.8b01466. 

Miess H, Jahanshah G, Brötz-Oesterhelt H, Willmann M, Peter S, Gross H. 2018. Draft Genome Sequence of the Extensively Drug-Resistant Pseudomonas aeruginosa Clinical Isolate TUEPA7472. Microbiol Resour Announc 7:e01055-18. 

Saising J, Nguyen MT, Härtner T, Ebner P, Al Mamun Bhuyan A, Berscheid A, Muehlenkamp M, Schäkermann S, Kumari N, Maier ME, Voravuthikunchai SP, Bandow J, Lang F, Brötz-Oesterhelt H, Götz F. 2018. Rhodomyrtone (Rom) is a membrane-active compound. Biochim Biophys Acta., 1860(5):1114-1124. 

Mokhlesi A, Stuhldreier F, Wex KW, Berscheid A, Hartmann R, Rehberg N, Sureechatchaiyan P, Chaidir C, Kassack M, Kalscheuer R, Brötz-Oesterhelt H, Wesselborg S, Stork B, Daletos G, Proksch P. 2017. Cyclic cystine-bridged peptides from the marine sponge Clathria basilana induce apoptosis in tumor cells and depolarize the bacterial cytoplasmic membrane. J Nat Prod., 80(11):2941-2952. 80(11):2941-2952.

Malik I, Brötz-Oesterhelt H. 2017. Conformational control of the bacterial Clp protease by natural product antibiotics. Nat. Prod. Rep., 34(7):815-831.

Raschig J, Mailänder-Sanchez D, Berscheid A, Berger J, Strömstedt AA, Courth L, Malek N, Brötz-Oesterhelt H, Wehkamp J. 2017. Redox dependent trapping and killing represent diverse antibacterial strategies of ubiquitously expressed human beta defensin 1 (hBD1). Plos Pathogens, 13(3):e1006261.

Schüller A, Matzner D, Lünse C, Wittmann V, Schumacher C, Unsleber S, Brötz-Oesterhelt H, Mayer C, Bierbaum G, Mayer G. 2017. "Activation of the glmS ribozyme confers bacterial growth inhibition." Chembiochem, 18(5):435-440.

Zipperer, A. , Konnerth, M.C., Laux. C., Berscheid, A., Janek, D., Weidenmaier, C., Burian, M., Schilling, N.A., Slavetinsky, C., Marschal, M., Willmann, M., Kalbacher, H., Schittek, B., Brötz-Oesterhelt, H., Grond, S., Peschel, A., Krismer, B. 2016. „Human commensals producing a novel antibiotic impair pathogen colonization.“ Nature 535(7613):511-6.

Famulla, K., P. Sass, I. Malik, T. Akopian, O. Kandror, M. Alber, B. Hinzen, H. Ruebsamen-Schaeff, R. Kalscheuer, A.L. Goldberg, H. Brötz-Oesterhelt. 2016. „Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease.” Mol Microbiol. 101(2):194-209.

Gersch, M., Famulla, K., Dahmen, M., Göbl, C., Malik, I., Richter, K., Korotkoc, V.S., Sass, P., Rübsamen-Schaeff, H., Madl, T, Brötz-Oesterhelt, H., and Sieber, S. 2015. „AAA+ chaperones and acyldepsipeptides activate ClpP via conformational control.” Nat. Commun. 6:6320.

Chen, H., Daletos, G., Abdel-Aziz, M.S., Thomy, D., Dai, H., Brötz-Oesterhelt, H., Lin, W., Proksch, P. 2015. „Inducing secondary metabolite production by the soil-dwelling fungus Aspergillus terreus through bacterial co-culture” Phytochem. Letters 12:35-41.

2010 - 2014

Hammerschmidt, L., Debbab, A., Ngocb, T.D., Wray, V., Perèz Hemphila, C., Lind, W., Brötz-Oesterhelt, H., Kassack, M., Proksch, P., Aly, A. H. 2014. „Polyketides from the mangrove-derived endophytic fungus Acremonium strictum.” Tetrahedron Lett. 55, 3463-3468.

Ola, A.R.B., Debbab, A., Kurtan, T., Brötz‐Oesterhelt, H., Aly, A.H., Proksch, P. 2014. “Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa.” Tetrahedron Lett. 55, 3147-3150. 3.

Ola, A.R.B., Debbab, A., Aly, A.H., Mandi, A., Zerfass, I., Hamacher, A., Kassack, M.U., Broetz-Oesterhelt, H., Kurtan, T., Proksch, P. 2014. “Absolute configuration and antibiotic activity of neosartorin from the endophytic fungus Aspergillus fumigatiaffinis.” Tetrahedron Letters (2014) 55: 1020-1023.

Wenzel, M., Chiriac, A. I., Otto, A., Zweytick, D., May, C., Schumacher, C., Gust, R., Bauke Albada, H., Penkova, M., Krämer, U., Erdmann, R., Metzler-Nolte, N., Straus, S., Bremer, E., Becher, D., Brötz-Oesterhelt, H., Sahl, H.-G. and Bandow, J. E. 2014. “Small cationic antimicrobial peptides delocalize peripheral membrane proteins.” Proc. Natl. Acad. Sci. (2014) doi:10.1073/pnas.1319900111.

Ola, A.R.B., Thomy, D., Lai, D., Brötz-Oesterhelt, H. and P. Proksch, H. “Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis.” J. Nat. Prod. 76, 2094-2099 (2013).

Sass, P., and H. Brötz-Oesterhelt, H. 2013. “Bacterial cell division as a target for new antibiotics.”Curr. Opin. Microbiol. 16, 522-530 (2013).

Brötz-Oesterhelt, H., and P. Sass. 2013. “Bacterial caseinolytic proteases as novel targets for antibacterial treatment.” Int J Med Microbiol. (2013), doi:pii: S1438-4221(13)00138-0. 10.1016/j.ijmm.2013.09.001.

Lai D., Brötz-Oesterhelt H., Müller W.E., Wray V., Proksch P. "Bioactive polyketides and alkaloids from Penicillium citrinum, a fungal endophyte isolated from Ocimum tenuiflorum." Fitoterapia. 91, 100-106 (2013).

Brötz-Oesterhelt, H. and P. Sass. Bacterial cell stress protein ClpP: A novel antibiotic target. In: Moonlighting cell stress proteins in microbial infections. B. Henderson (Ed.), Springer. “Moonlighting Cell Stress Proteins in Microbial Infections” in the series Heat Shock Proteins 7:375-385. Springer Netherlands, DOI 10.1007/978-94-007-6787-4_24, Print ISBN 978-94-007-6786-7, Online ISBN 978-94-007-6787-4 (2013).

Bara, R.; I. Zerfass, A.H. Aly, H. Goldbach-Gecke, V. Raghavan, P. Sass, A. Mándi, V. Wray, P.L. Polavarapu, A. Pretsch, W. Lin, T. Kurtán, A. Debbab, H. Brötz-Oesterhelt, and P. Proksch. 2013. “Atropisomeric dihydroanthracenones as inhibitors of multiresistant Staphylococcus aureus” J. Med. Chem., 56, 3257-3272 (2013).

Schiefer, A., J. Vollmer, C. Lämmer, S. Specht, C. Lentz, H. Ruebsamen-Schaeff, H. Brötz-Oesterhelt, A. Hoerauf und K. Pfarr. The peptidase ClpP of Wolbachia endobacteria is a novel target for drug development against filarial infections. J. Antimicrob. Chemother. 68, 1790-1800 (2013).

Lowth, B. R., Kirstein-Miles, J., Saiyet, T., Brötz-Oesterhelt, H., Morimoto, R. I., Truscott, K. N. and D. A. Dougan. Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein ClpX. J. Struct. Biol. 179, 193-201 (2012).

Müller, A., D. Münch, Y. Schmidt, K. Reder-Christ, G. Schiffer, G. Bendas, H. Gross, H.-G. Sahl, T. Schneider, H. Brötz-Oesterhelt. The lipodepsipeptide empedopeptin inhibits cell wall biosynthesis through Ca2+-dependent complex formation with peptidoglycan precursors. J Biol Chem. 287, 20270-20280 (2012).

Sass, P. and H. Brötz-Oesterhelt. Bacterial stress responses to antimicrobial agents. In: Stress Responses in Foodborne Microorganisms, in the Series “Advances in Food Microbiology and Food Safety”. A. De Souza Sant’ana (Ed.). (2012) Nova Science Publishers Inc. ISBN: 978-1-61122-810-6.

Sass, P., M. Josten, K. Famulla, G. Schiffer, H.-G. Sahl, L. Hamoen and H. Brötz-Oesterhelt. Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ. Proc. Natl. Acad. Sci. 108, 17474-17479 (2011).

Brötz-Oesterhelt, H. and P. Sass. Post-genomic strategies in antibacterial drug discovery. Future Microbiology 5, 1553-1579 (2010).

Lee B.-G., E. Y. Park, K.-E. Lee, H. Jeon, K. H. Sung, H. Paulsen, H. Rübsamen-Schaeff, H. Brötz-Oesterhelt, and H. K. Song. Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. Nature Struct. Mol. Biol. 17, 471-478 (2010).

2005 - 2009

Kirstein, J., A. Hoffmann, H. Lilie, R. Schmidt, H. Rübsamen-Waigmann, H. Brötz-Oesterhelt, A. Mogk and K. Turgay. The antibiotic ADEP reprograms ClpP, switching it from a regulated to an uncontrolled protease. EMBO Molecular Medicine 1, 37-49 (2009).

Streker, K., T. Schäfer, C. Freiberg, H. Brötz-Oesterhelt, J. Hacker, H. Labischinski and K. Ohlsen. In vitro and in vivo validation of ligA and tarI as essential targets in Staphylococcus aureus. Antimicrob. Agents Chemother. 52, 4470-4474 (2008).

Brötz-Oesterhelt, H. and N. Brunner. How many modes of action should an antibiotic have? Curr. Opin. Pharmacol. 8:1-10 (2008).

Beyer, D., H-P. Kroll and H. Brötz-Oesterhelt. Methods to assay inhibitors of tRNA synthetase activity. In Methods in Molecular Medicine. Vol. 142, New antibiotic targets. S. Champney (Ed.), Humana Press, 53-61 (2008).

B. Hinzen, S. Raddatz, H. Paulsen, T. Lampe, A. Schumacher, D. Häbich, V. Hellwig, J. Benet-Buchholz, R. Endermann, H. Labischinski and H. Brötz-Oesterhelt. Medicinal chemistry optimization of acyldepsipeptides of the enopeptin class antibiotics. Chem. Med. Chem. 1, 689-693 (2006).

Labischinski H., C. Freiberg and H. Brötz-Oesterhelt. New Antibiotics. In: Pathogenomics – Genome analysis of pathogenic microbes. J. Hacker and U. Dobrindt (Ed.), Wiley VCH, 505-531 (2005).

Brötz-Oesterhelt, H., D. Beyer, H.-P. Kroll, R. Endermann, C. Ladel, W. Schroeder, B. Hinzen, S. Raddatz, H. Paulsen, K. Henninger, J. E. Bandow, H.-G. Sahl and H. Labischinski. Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nature Medicine. 11, 1082-1087 (2005).

Freiberg, C. and H. Brötz-Oesterhelt. Functional genomics in antibacterial drug discovery. Drug Discov. Today. 10, 927-935 (2005).

Brötz-Oesterhelt H., J. E. Bandow and H. Labischinski. Bacterial proteomics and its role in antibacterial drug discovery. Mass. Spec. Rev. 24, 549-565 (2005).

2000 - 2004

Freiberg, C., H. Brötz-Oesterhelt and H. Labischinski. The impact of transcriptome and proteome analyses on antibiotic drug discovery. Curr. Opin. Microbiol. 7, 451–459 (2004).

J. Pohlmann and Brötz-Oesterhelt H. New aminoacyl-tRNA synthetase inhibitors as antibacterial agents. Current Drug Targets – Infectious Disorders 4, 261-272 (2004).

Brötz-Oesterhelt, H. Antibiotics -Actions, Origins, Resistance. Book review. Angew. Chem. Int. Ed. 43, 2879-2880 (2004).

Beyer, D., H. P. Kroll, R. Endermann, G. Schiffer, S. Siegel, M. Bauser, J. Pohlmann, M. Brands, K. Ziegelbauer, D. Häbich and H. Brötz-Oesterhelt. New class of phenylalanyl-tRNA synthetase inhibitors with high potency and broad spectrum activity. Antimicrob. Agents Chemother. 48, 525-532 (2004).

Brötz-Oesterhelt, H., I. Knezevic, S. Bartel, T. Lampe, U. Warnecke-Eberz, K. Ziegelbauer, D. Häbich and H. Labischinski. Specific and potent inhibition of NAD+-dependent DNA ligase by pyridochromanones. J. Biol. Chem. 278, 39435-39442 (2003).

Bandow, J. E., D. Becher, K. Büttner, F. Hochgräfe, C. Freiberg, H. Brötz and M. Hecker. The role of peptide deformylase in protein biosynthesis: A proteomic study. Proteomics, 3, 299-306 (2003).

Bandow, J. E., H. Brötz, L. I. O. Leichert, H. Labischinski and M. Hecker. A proteomic approach to understanding antibiotic action. Antimicrob. Agents Chemother., 47, 948-955 (2003).

Bandow, J. E., H. Brötz and M. Hecker: B. subtilis tolerance of moderate concentrations of rifampicin involves the sB-dependent general and multiple stress response. J. Bacteriol., 184, 459-467 (2002).

Freiberg, C., B. Wieland, F. Spaltmann, K. Ehlert, H. Brötz and H. Labischinski: Identification of novel essential Escherichia coli genes conserved among pathogenic bacteria. J. Mol. Microbiol. Biotechnol. 3, 483-489 (2001).

Brötz, H. and H.-G. Sahl: New insights into the mechanism of action of lantibiotics - diverse biological effects by binding to the same molecular target. J. Antibiot. Chemother. 46, 1-6 (2000).

1995 - 1999

Brötz, H., M. Josten, I. Wiedemann, U. Schneider, G. Bierbaum and H.-G. Sahl: Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics. Mol. Microbiol. 30, 317-328 (1998).

Brötz, H., G. Bierbaum, K. Leopold, P. E. Reynolds and H.-G. Sahl: The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob. Agents Chemother., 42, 154-160 (1998).

Brötz, H., G. Bierbaum, P. E. Reynolds and H.-G. Sahl: The lantibiotic mersacidin inhibits peptidoglycan synthesis at the level of transglycosylation. Eur. J. Biochem., 246, 193-199 (1997).

Molitor E., C. Kluczny, H. Brötz, G. Bierbaum, R. Jack and H.-G. Sahl: Effects of the lantibiotic mersacidin on the morphology of staphylococci. Zbl. Bakt., 284, 318-328 (1996).

Brötz, H., G. Bierbaum and H.-G. Sahl: Modes of action of lantibiotics. In: Recent Research and Development in Antimicrobial Agents and Chemotherapy, G. Pandalai (Ed.), Research Signpost, Trivandrum, Vol. 1, 125-134 (1996).

Bierbaum, G., H. Brötz, H.-P. Koller and H.-G. Sahl: Cloning, sequencing and production of the lantibiotic mersacidin. FEMS Microbiol. Lett., 127, 121-126 (1995).

Brötz, H., G. Bierbaum, A. Markus, E. Molitor and H.-G. Sahl: Mode of action of the lantibiotic mersacidin: Inhibition of peptidoglycan biosynthesis via a novel mechanism? Antimicrob. Agents Chemother., 39, 714-719 (1995).



Klenke B, Wiegand I, Schiffer G, Brötz-Oesterhelt H, Maiti S, Khan J, Reddy A, Yang Z, Hena M, Jia G, Ligong O, Liang H, Yip J, Gao C, Tajammul S, Mohammad R, Biswajeet G. WO/2013/110643, PCT/EP2013/051217. Amidin substituted beta-lactam compounds, their preparation and use as antibacterial agents

Lerchen, H.-G., G. Schiffer, H. Brötz-Oesterhelt, A. Mayer-Bartschmid, S. Eckermann, C. Freiberg und D. Häbich. WO 2007/059908. Novel cyclic iminopeptide derivatives and a process for preparing cyclic iminopeptide derivatives.

Lerchen, H.-G., G. Schiffer, H. Brötz-Oesterhelt, A. Mayer-Bartschmid, S. Eckermann, C. Freiberg, R. Endermann, J. Schuhmacher, H. Meier, N. Svenstrup, S. Seip, M. Gehling und D. Häbich. WO 2006/103010. Cyclic iminopeptide derivatives.

Hinzen, B., H. Brötz, R. Endermann, K. Henninger, H. Paulsen, S. Raddatz und S. Anlauf. DE 10308107. Mono-ungesättigte Acyl-Verbindungen.

Hinzen, B., H. Brötz, R. Endermann, K. Henninger, H. Paulsen, S. Raddatz, T. Lampe, V. Hellwig, and A. Schumacher. DE 10219225. Serinderivate.

Bauser, M., D. Beyer, H. Brötz, R. Endermann, M. Hauswald, H.-P. Kroll, J. Pohlmann, S. Siegel, G. Schiffer. DE 10155684. Thiazolharnstoffe.

Hinzen, B., H. Brötz, R. Endermann, K. Henninger, H. Paulsen, S. Raddatz, T. Lampe, V. Hellwig, A. Schumacher. WO-03024996-A2 Antibacterial macrocycles.

Brötz, H., K. Ehlert, C. Freiberg, F. Spaltmann, B. Wieland und H. Labischinski. WO-0/61792: Novel essentiell bacterial genes and their proteins.