Interfaculty Institute of Microbiology and Infection Medicine

Publications

Department Microbial Bioactive Compounds

2020 to date

Senges CHR, Stepanek JJ, Wenzel M, Raatschen N, Ay Ü, Märtens Y, Prochnow P, Vázquez Hernández M, Yayci A, Schubert B, Janzing NBM, Warmuth HL, Kozik M, Bongard J, Alumasa JN, Albada B, Penkova M, Lukežič T, Sorto NA, Lorenz N, Miller R, Zhu B, Benda M, Stülke J, Schäkermann S, Leichert LI, Scheinpflug K, Brötz-Oesterhelt H, Hertweck C, Shaw JT, Petković H, Brunel JM, Keiler KC, Metzler-Nolte N, Bandow JE. Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation. Antimicrob Agents Chemother. 2020 Oct 12:AAC.01373-20. Epub ahead of print. PMID: 33046497. doi: 10.1128/AAC.01373-20.

Silber N, Pan S, Schäkermann S, Mayer C, Brötz-Oesterhelt H, Sass P. Cell division protein FtsZ is unfolded for N-terminal degradation by antibiotic-activated ClpP. mBio 11:e01006-20. doi.org/10.1128/mBio.01006-20 (2020).

Bafna JA, Sans-Serramitjana E, Acosta-Gutiérrez S, Bodrenko IV, Hörömpöli D, Berscheid A, Brötz-Oesterhelt H, Winterhalter M, Ceccarelli M. Kanamycin Uptake into Escherichia coli Is Facilitated by OmpF and OmpC Porin Channels Located in the Outer Membrane. ACS Infect. Dis. 2020. doi: 10.1021/acsinfecdis.0c00102. 

Malik IT, Pereira R, Vielberg MT, Mayer C, Straetener J, Thomy D, Famulla K, Castro H, Sass P, Groll M, Brötz-Oesterhelt H. Functional characterisation of ClpP mutations conferring resistance to acyldepsipeptide antibiotics in Firmicutes. Chembiochem. 2020. doi: 10.1002/cbic.201900787. 

Chen J, Frediansyah A, Männle D, Straetener J, Brötz-Oesterhelt H, Ziemert N, Kaysser L, Gross H. Terpenibactins A-C, new nocobactin derivatives with antimuscarinic activity, revealed by genome mining of Nocardia terpenica IFM 0406. Chembiochem. 2020. doi: 10.1002/cbic.202000062. 

Kossack R, Breinlinger S, Nguyen T, Moschny J, Straetener J, Berscheid A, Brötz-Oesterhelt H, Enke H, Schirmeister T, Niedermeyer THJ. Nostotrebin 6 related cyclopentenediones and δ-lactones with broad activity spectrum isolated from the cultivation medium of the cyanobacterium Nostoc sp. CBT1153 J. Nat. Prod. doi: 10.1021/acs.jnatprod.9b00885. 

2015-2019

Eyermann B, Meixner M, Brötz-Oesterhelt H, Antes I, Sieber SA. Acyldepsipeptide probes facilitate specific detection of caseinolytic protease P independent of its oligomeric and activity state. Chembiochem. doi: 10.1002/cbic.201900477. 

Lennings J, Makhlouf M, Olejnik P, Mayer C, Brötz-Oesterhelt H, Schwarz S. Environmental and cellular factors affecting the localization of T6SS proteins in Burkholderia thailandensis. Int J Med Microbiol. 2019 Sep;309(6):151335. doi: 10.1016/j.ijmm.2019.151335. (2019).

Thomy D, Culp E, Adamek M, Cheng EY, Ziemert N, Wright GD, Sass P, Brötz-Oesterhelt H. The ADEP biosynthetic gene cluster in Streptomyces hawaiiensis NRRL 15010 reveals an accessory clpP gene as a novel antibiotic resistance factor. Appl. Environ. Microbiol. doi:10.1128/AEM.01292-19 (2019).  [For a free e-print, please contact us]

Mayer C, Sass P, Brötz-Oesterhelt H. Consequences of dosing and timing on the antibacterial effects of ADEP antibiotics. Int J Med Microbiol. 151329. doi: 10.1016/j.ijmm.2019.151329 (2019).

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).

 

Patents

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.