β-Lactones as Specific Inhibitors of ClpP Attenuate the Production of Extracellular Virulence Factors of Staphylococcus aureus
Abstract
To approach the daunting problem of multidrug resistant bacterial pathogens, a multidisciplinary chemical proteomic strategy was applied and functionalized beta-lactones were identified as potent, cell permeable inhibitors for specific and selective targeting of the key virulence regulator complex ClpP in S. aureus and methicillin resistant S. aureus (MRSA) strains. ClpP represents the central protease complex responsible for the activation of numerous virulence factors including many with devastating effects for human health such as hemolysins, proteases, lipases, and DNases. Although the crucial role of this enzyme was validated by genetic knockouts, no inhibitor has been reported to date. In fact, our most potent inhibitor was able to completely abolish hemolytic and proteolytic activities and showed a dramatic decrease in the activities of virulence associated lipases and DNases. These effects were also observed in a multiresistant strain emphasizing the potential value of such compounds. Targeting this virulence factor may therefore likely represent an attractive strategy for neutralizing the harmful effects of bacterial pathogens and help the host immune response to eliminate the disarmed bacteria. Since ClpP is not essential for viability and highly conserved in many pathogens, our strategy could represent a global approach for the treatment of infectious diseases without the pressing problem of antibiotic pressure and resistance development.
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These nucleophilic centers are also present in DNA and other biologically relevant compounds, such as glutathione.
“These nucleophilic centers are also present in DNA and other biologically relevant compounds, such as glutathione.116–121”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [116]
Cites
Staphylococcus aureus Infections
Lowy, F. D. (1998) · New England Journal of Medicine · doi:10.1056/nejm199808203390806 · Cited by 6,018 · see citing works
Targeting virulence: a new paradigm for antimicrobial therapy
Clatworthy, A. E., Pierson, E. R., & Hung, D. T. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.24 · Cited by 1,410 · see citing works
Speers, A. E., Adam, G. C., & Cravatt, B. F. (2003) · Journal of the American Chemical Society · doi:10.1021/ja034490h · Cited by 955 · see citing works
Mechanism-Based Profiling of Enzyme Families
Evans, M. J., & Cravatt, B. F. (2006) · Chemical Reviews · doi:10.1021/cr050288g · Cited by 568 · see citing works
Dysregulation of bacterial proteolytic machinery by a new class of antibiotics
Brötz-Oesterhelt, H., Beyer, D., Kroll, H.-P., Endermann, R., Ladel, C., Schroeder, W., Hinzen, B., Raddatz, S., Paulsen, H., Henninger, K., et al. (2005) · Nature Medicine · doi:10.1038/nm1306 · Cited by 505 · see citing works
Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and virulence
Frees, D., Qazi, S. N. A., Hill, P. J., & Ingmer, H. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03524.x · Cited by 328 · see citing works
Michel, A., Agerer, F., Hauck, C. R., Herrmann, M., Ullrich, J., Hacker, J. H., & Ohlsen, K. (2006) · Journal of Bacteriology · doi:10.1128/jb.00074-06 · Cited by 214 · see citing works
Specific roles of alpha-toxin and beta-toxin during Staphylococcus aureus corneal infection
O’Callaghan, R. J., Callegan, M. C., Moreau, J. M., Green, L. C., Foster, T. J., Hartford, O. M., Engel, L. S., & Hill, J. M. (1997) · Infection and Immunity · doi:10.1128/iai.65.5.1571-1578.1997 · Cited by 195 · see citing works
Böttcher, T., & Sieber, S. A. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200705768 · Cited by 181 · see citing works
Self-citationBurlak, C., Hammer, C. H., Robinson, M.-A., Whitney, A. R., Mcgavin, M. J., Kreiswirth, B. N., & DeLeo, F. R. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00858.x · Cited by 177 · see citing works
[23] Endopeptidase Clp: ATP-dependent Clp protease from Escherichia coli
Maurizi, M. R., Thompson, M. W., Singh, S. K., & Kim, S. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)44025-5 · Cited by 154 · see citing works
The hemolysins of Staphylococcus aureus
Wiseman, G. M. (1975) · Bacteriological Reviews · doi:10.1128/br.39.4.317-344.1975 · Cited by 107 · see citing works
Walev, I., Weller, U., Strauch, S., Foster, T. J., & Bhakdi, S. C. (1996) · Infection and Immunity · doi:10.1128/iai.64.8.2974-2979.1996 · Cited by 98 · see citing works
Interference ofStaphylococcus aureus lipase with human granulocyte function
Rollof, J., Braconier, J. H., Söderström, C., & Nilsson‐Ehle, P. (1988) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf01962601 · Cited by 87 · see citing works
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Sorted by citations
Target Identification for Small Bioactive Molecules: Finding the Needle in the Haystack
Ziegler, S., Pries, V., Hedberg, C., & Waldmann, H. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201208749 · Cited by 466 · see citing works
Strategies for Discovering and Derisking Covalent, Irreversible Enzyme Inhibitors
Johnson, D. S., Weerapana, E., & Cravatt, B. F. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.10.21 · Cited by 387 · see citing works
Enzyme Inhibitor Discovery by Activity-Based Protein Profiling
Niphakis, M. J., & Cravatt, B. F. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035708 · Cited by 366 · see citing works
Activity-based Proteomics of Enzyme Superfamilies: Serine Hydrolases as a Case Study
Simon, G. M., & Cravatt, B. F. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.097600 · Cited by 327 · see citing works
Electrophilic natural products and their biological targets
Gersch, M., Kreuzer, J., & Sieber, S. A. (2012) · Natural Product Reports · doi:10.1039/c2np20012k · Cited by 282 · see citing works
Self-citationBacterial proteases, untapped antimicrobial drug targets
Culp, E., & Wright, G. D. (2017) · The Journal of Antibiotics · doi:10.1038/ja.2016.138 · Cited by 244 · see citing works
Yang, P., Liu, K., Ngai, M. H., Lear, M. J., Wenk, M. R., & Yao, S. Q. (2009) · Journal of the American Chemical Society · doi:10.1021/ja907716f · Cited by 230 · see citing works
Natural Products and Their Biological Targets: Proteomic and Metabolomic Labeling Strategies
Böttcher, T., Pitscheider, M., & Sieber, S. A. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.200905352 · Cited by 213 · see citing works
Self-citationRaju, R. M., Unnikrishnan, M., Rubin, D. H. F., Krishnamoorthy, V., Kandror, O., Akopian, T. N., Goldberg, A. L., & Rubin, E. J. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002511 · Cited by 197 · see citing works
Proteases and protease inhibitors in infectious diseases
Agbowuro, A. A., Huston, W. M., Gamble, A. B., & Tyndall, J. D. A. (2017) · Medicinal Research Reviews · doi:10.1002/med.21475 · Cited by 188 · see citing works
Frees, D., Gerth, U., & Ingmer, H. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.11.009 · Cited by 172 · see citing works
Proteases in bacterial pathogenesis
Ingmer, H., & Brøndsted, L. (2009) · Research in Microbiology · doi:10.1016/j.resmic.2009.08.017 · Cited by 172 · see citing works
Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis
Lakemeyer, M., Zhao, W., Mandl, F. A. M., Hammann, P., & Sieber, S. A. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201804971 · Cited by 170 · see citing works
Self-citationBacterial Proteases and Virulence
Frees, D., Brøndsted, L., & Ingmer, H. (2013) · Subcellular Biochemistry · doi:10.1007/978-94-007-5940-4_7 · Cited by 159 · see citing works
The Role of ClpP Protease in Bacterial Pathogenesis and Human Diseases
Bhandari, V., Wong, K. S., Zhou, J. L., Mabanglo, M. F., Batey, R. A., & Houry, W. A. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00124 · Cited by 157 · see citing works
Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy
Nouri, K., Feng, Y., & Schimmer, A. D. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03062-z · Cited by 156 · see citing works
Sintim, H. O., Smith, J. A. I., Wang, J., Nakayama, S., & Yan, L. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.10.185 · Cited by 148 · see citing works
AAA+ chaperones and acyldepsipeptides activate the ClpP protease via conformational control
Gersch, M., Famulla, K., Dahmen, M., Göbl, C., Malik, I. T., Richter, K., Korotkov, V. S., Saß, P., Rübsamen‐Schaeff, H., Madl, T., et al. (2015) · Nature Communications · doi:10.1038/ncomms7320 · Cited by 134 · see citing works
Self-citationClpP Protease, a Promising Antimicrobial Target
Moreno-Cinos, C., Goossens, K., Salado, I. G., der Veken, P. V., Winter, H. L. D., & Augustyns, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092232 · Cited by 126 · see citing works
β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium
Fisher, J. F., & Mobashery, S. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01010 · Cited by 127 · see citing works
Wang, J., Gao, L., Lee, Y. M., Kalesh, K., Ong, Y. S., Lim, J., Jee, J., Sun, H., Lee, S. S., Hua, Z., et al. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.01.010 · Cited by 122 · see citing works
Rusch, M., Zimmermann, T. J., Bürger, M., Dekker, F. J., Görmer, K., Triola, G., Brockmeyer, A., Janning, P., Böttcher, T., Sieber, S. A., et al. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201102967 · Cited by 121 · see citing works
Self-citationTwo Spx Proteins Modulate Stress Tolerance, Survival, and Virulence in Streptococcus mutans
Kajfasz, J. K., Rivera-Ramos, I., Abranches, J., Martinez, A. R., Rosalen, P. L., Derr, A. M., Quivey, R. G., & Lemos, J. A. C. (2010) · Journal of Bacteriology · doi:10.1128/jb.00028-10 · Cited by 114 · see citing works
Progress and prospects for small-molecule probes of bacterial imaging
Kocaoglu, O., & Carlson, E. E. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2109 · Cited by 111 · see citing works
Hackl, M. W., Lakemeyer, M., Dahmen, M., Glaser, M., Pahl, A., Lorenz‐Baath, K., Menzel, T., Sievers, S., Böttcher, T., Antes, I., et al. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b03084 · Cited by 111 · see citing works
Self-citationWang, J., Tan, X. F., Nguyễn, V. S., Yang, P., Zhou, J., Gao, M., Li, Z., Lim, T. K., He, Y., Ong, C. S., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.029793 · Cited by 109 · see citing works
Bacterial proteolytic complexes as therapeutic targets
Raju, R. M., Goldberg, A. L., & Rubin, E. J. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3846 · Cited by 105 · see citing works
Identification of a S. aureus virulence factor by activity-based protein profiling (ABPP)
Lentz, C. S., Sheldon, J. R., Crawford, L. A., Cooper, R. L., Garland, M., Amieva, M. R., Weerapana, E., Skaar, E. P., & Bogyo, M. S. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0060-1 · Cited by 102 · see citing works
Role of Clp Proteins in Expression of Virulence Properties ofStreptococcus mutans
Kajfasz, J. K., Martinez, A. R., Rivera-Ramos, I., Abranches, J., Koo, H., Quivey, R. G., & Lemos, J. A. C. (2009) · Journal of Bacteriology · doi:10.1128/jb.01609-08 · Cited by 96 · see citing works
The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum
Bakkouri, M. E., Pow, A., Mulichak, A. M., Cheung, K. L. Y., Artz, J. D., Amani, M., Fell, S. M., de Koning‐Ward, T. F., Goodman, C. D., McFadden, G. I., et al. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.09.051 · Cited by 91 · see citing works
Böttcher, T., & Sieber, S. A. (2010) · Journal of the American Chemical Society · doi:10.1021/ja909150y · Cited by 88 · see citing works
Self-citationCarney, D. W., Schmitz, K. R., Truong, J. V., Sauer, R. T., & Sello, J. K. (2014) · Journal of the American Chemical Society · doi:10.1021/ja410385c · Cited by 87 · see citing works
Bacterial caseinolytic proteases as novel targets for antibacterial treatment
Brötz‐Oesterhelt, H., & Saß, P. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.09.001 · Cited by 85 · see citing works
Mitochondrial matrix proteases as novel therapeutic targets in malignancy
Goard, C. A., & Schimmer, A. D. (2013) · Oncogene · doi:10.1038/onc.2013.228 · Cited by 82 · see citing works
β-Lactams and β-lactones as activity-based probes in chemical biology
Böttcher, T., & Sieber, S. A. (2012) · MedChemComm · doi:10.1039/c2md00275b · Cited by 82 · see citing works
Self-citationZeiler, E., Braun, N., Böttcher, T., Kastenmüller, A., Weinkauf, S., & Sieber, S. A. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201104391 · Cited by 82 · see citing works
Self-citationLehmann, J., Cheng, T., Aggarwal, A., Park, A. S., Zeiler, E., Raju, R. M., Akopian, T., Kandror, O., Bach, N., Sacchettini, J., et al. (2017) · Angewandte Chemie · doi:10.1002/anie.201709365 · Cited by 68 · see citing works
Self-citationSuppression of Staphylococcus aureus virulence by a small-molecule compound
Gao, P., Ho, P., Yan, B., Sze, K. H., DAVIES, J. E., & Kao, R. Y. T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720520115 · Cited by 76 · see citing works
Mabanglo, M. F., & Houry, W. A. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101781 · Cited by 77 · see citing works
Activity‐Based Protein Profiling: Recent Advances in Probe Development and Applications
Yang, P., & Liu, K. (2015) · ChemBioChem · doi:10.1002/cbic.201402582 · Cited by 76 · see citing works
Schmitz, K. R., & Sauer, R. T. (2014) · Molecular Microbiology · doi:10.1111/mmi.12694 · Cited by 76 · see citing works
Leodolter, J., Warweg, J., & Weber-Ban, E. U. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125345 · Cited by 75 · see citing works
Antibacterial Activity of and Resistance to Small Molecule Inhibitors of the ClpP Peptidase
Compton, C. L., Schmitz, K. R., Sauer, R. T., & Sello, J. K. (2013) · ACS Chemical Biology · doi:10.1021/cb400577b · Cited by 74 · see citing works
Keller, L. J., Babin, B. M., Lakemeyer, M., & Bogyo, M. S. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.10.007 · Cited by 70 · see citing works
Gersch, M., List, A., Groll, M., & Sieber, S. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.336222 · Cited by 70 · see citing works
Self-citationGersch, M., Kolb, R., Alte, F., Groll, M., & Sieber, S. A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4082793 · Cited by 67 · see citing works
Self-citationZeiler, E., List, A., Alte, F., Gersch, M., Wachtel, R., Poręba, M., Drąg, M., Groll, M., & Sieber, S. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219125110 · Cited by 66 · see citing works
Self-citationRegulation of host hemoglobin binding by the Staphylococcus aureus Clp proteolytic system
Farrand, A. J., Reniere, M. L., Ingmer, H., Frees, D., & Skaar, E. P. (2013) · Journal of Bacteriology · doi:10.1128/jb.00505-13 · Cited by 56 · see citing works
Structurally Refined β‐Lactones as Potent Inhibitors of Devastating Bacterial Virulence Factors
Böttcher, T., & Sieber, S. A. (2009) · ChemBioChem · doi:10.1002/cbic.200800743 · Cited by 63 · see citing works
Self-citationVitale, G. A., Geibel, C., Minda, V., Wang, M., Aron, A. T., & Petras, D. (2024) · Natural Product Reports · doi:10.1039/d3np00050h · Cited by 66 · see citing works
The Mechanism of Caseinolytic Protease (ClpP) Inhibition
Gersch, M., Gut, F., Korotkov, V. S., Lehmann, J., Böttcher, T., Rusch, M., Hedberg, C., Waldmann, H., Klebe, G., & Sieber, S. A. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201204690 · Cited by 61 · see citing works
Self-citationFighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research
Süßmuth, R. D., Kulike-Koczula, M. D., Gao, P., & Kosol, S. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202414325 · Cited by 65 · see citing works
Xie, F., Zhang, Y., Li, G., Zhou, L., Liu, S., & Wang, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053600 · Cited by 60 · see citing works
Development and characterization of improved β-lactone-based anti-virulence drugs targeting ClpP
Zeiler, E., Korotkov, V. S., Lorenz‐Baath, K., Böttcher, T., & Sieber, S. A. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.07.047 · Cited by 59 · see citing works
Self-citationWang, B., Zhao, A., Novick, R. P., & Muir, T. W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506030112 · Cited by 58 · see citing works
The development of small-molecule modulators for ClpP protease activity
Ye, F., Li, J., & Yang, C. (2016) · Molecular BioSystems · doi:10.1039/c6mb00644b · Cited by 58 · see citing works
Ye, F., Zhang, J., Liu, H., Hilgenfeld, R., Zhang, R., Kong, X., Li, L., Lu, J., Zhang, X., Li, D., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.452714 · Cited by 57 · see citing works
Proteomic signatures in antibiotic research
Wenzel, M., & Bandow, J. E. (2011) · PROTEOMICS · doi:10.1002/pmic.201100046 · Cited by 57 · see citing works
Florentin, A., Cobb, D. W., Fishburn, J. D., Cipriano, M. J., Kim, P. S., Fierro, M. A., Striepen, B., & Muralidharan, V. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.081 · Cited by 52 · see citing works
Rathore, S., Sinha, D., Asad, M., Böttcher, T., Afrin, F., Chauhan, V. S., Gupta, D. K., Sieber, S. A., & Mohmmed, A. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07251.x · Cited by 50 · see citing works
Self-citationActivity-Based Protein Profiling for Natural Product Target Discovery
Krysiak, J. M., & Breinbauer, R. (2011) · Topics in current chemistry · doi:10.1007/128_2011_289 · Cited by 50 · see citing works
Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP
Wei, B., Zhang, T., Wang, P., Pan, Y., Li, J., Chen, W., Zhang, M., Ji, Q., Wu, W., Lan, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34753-0 · Cited by 51 · see citing works
Identifizierung der Zielproteine bioaktiver Verbindungen: Die Suche nach der Nadel im Heuhaufen
Ziegler, S., Pries, V., Hedberg, C., & Waldmann, H. (2013) · Angewandte Chemie · doi:10.1002/ange.201208749 · Cited by 45 · see citing works
Luo, J., Zeng, B., Tao, C., Lu, M., & Ren, G. (2020) · PeerJ · doi:10.7717/peerj.8754 · Cited by 44 · see citing works
Ju, Y., An, Q., Zhang, Y., Sun, K., Bai, L., & Luo, Y. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.05.014 · Cited by 44 · see citing works
A New Class of Rhomboid Protease Inhibitors Discovered by Activity-Based Fluorescence Polarization
Wolf, E. V., Zeißler, A., Vosyka, O., Zeiler, E., Sieber, S. A., & Verhelst, S. H. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072307 · Cited by 43 · see citing works
Self-citationBöttcher, T., Pitscheider, M., & Sieber, S. A. (2010) · Angewandte Chemie · doi:10.1002/ange.200905352 · Cited by 43 · see citing works
Self-citationFetzer, C., Korotkov, V. S., Thänert, R., Lee, K. M., Neuenschwander, M., von Kries, J. P., Medina, E., & Sieber, S. A. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201708454 · Cited by 43 · see citing works
Self-citationYang, P., Liu, K., Zhang, C., Chen, G. Y. J., Shen, Y., Ngai, M. H., Lear, M. J., & Yao, S. Q. (2011) · Chemistry - An Asian Journal · doi:10.1002/asia.201100306 · Cited by 41 · see citing works
Discovery of a Potent Inhibitor Class with High Selectivity toward Clostridial Collagenases
Schönauer, E., Kany, A. M., Haupenthal, J., Hüsecken, K., Hoppe, I. J., Voos, K., Yahiaoui, S., Elsässer, B., Ducho, C., Brandstetter, H., et al. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b06935 · Cited by 41 · see citing works
A β‐Lactone‐Based Antivirulence Drug Ameliorates Staphylococcus aureus Skin Infections in Mice
Weinandy, F., Lorenz‐Baath, K., Korotkov, V. S., Böttcher, T., Sethi, S., Chakraborty, T., & Sieber, S. A. (2014) · ChemMedChem · doi:10.1002/cmdc.201300325 · Cited by 40 · see citing works
Self-citationSzamosvári, D., Reichle, V. F., Jureschi, M., & Böttcher, T. (2016) · Chemical Communications · doi:10.1039/c6cc06295d · Cited by 40 · see citing works
Self-citationCharacterization of Gain-of-Function Mutant Provides New Insights into ClpP Structure
Ni, T., Ye, F., Liu, X., Zhang, J., Liu, H., Li, J., Zhang, Y., Sun, Y.-Q., Wang, M., Luo, C., et al. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00390 · Cited by 38 · see citing works
Mabanglo, M. F., Leung, E., Vahidi, S., Seraphim, T. V., Eger, B. T., Bryson, S., Bhandari, V., Zhou, J. L., Mao, Y.-Q., Rizzolo, K., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0656-3 · Cited by 38 · see citing works
Global Inventory of ClpP- and ClpX-Regulated Proteins in Staphylococcus aureus
Kirsch, V. C., Fetzer, C., & Sieber, S. A. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c00668 · Cited by 38 · see citing works
Self-citationFux, A., Korotkov, V. S., Schneider, M., Antes, I., & Sieber, S. A. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.10.007 · Cited by 35 · see citing works
Self-citationFlorentin, A., Stephens, D. R., Brooks, C. F., Baptista, R. P., & Muralidharan, V. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1919501117 · Cited by 37 · see citing works
Tackling Antimicrobial Resistance by Exploring New Mechanisms of Antibiotic Action
de Opitz, C. L. M., & Saß, P. (2020) · Future Microbiology · doi:10.2217/fmb-2020-0048 · Cited by 37 · see citing works
β‐Lactones Decrease the Intracellular Virulence of Listeria monocytogenes in Macrophages
Böttcher, T., & Sieber, S. A. (2009) · ChemMedChem · doi:10.1002/cmdc.200900157 · Cited by 37 · see citing works
Self-citationAAA+ Machines of Protein Destruction in Mycobacteria
Thomas, A. A., & Dougan, D. A. (2017) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2017.00049 · Cited by 36 · see citing works
Design and synthesis of tailored human caseinolytic protease P inhibitors
Gronauer, T. F., Mandl, M. M., Lakemeyer, M., Hackl, M. W., Meßner, M., Korotkov, V. S., Pachmayr, J., & Sieber, S. A. (2018) · Chemical Communications · doi:10.1039/c8cc05265d · Cited by 36 · see citing works
Self-citationα-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease
Moreno-Cinos, C., Sassetti, E., Salado, I. G., Witt, G., Benramdane, S., Reinhardt, L., Cruz, C. D., Joossens, J., der Veken, P. V., Brötz‐Oesterhelt, H., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01466 · Cited by 35 · see citing works
Cormio, A., Sanguedolce, F., Pesce, V., & Musicco, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126228 · Cited by 34 · see citing works
Small-Molecule Potentiators for Conventional Antibiotics against Staphylococcus aureus
Vermote, A., & Calenbergh, S. V. (2017) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00084 · Cited by 33 · see citing works
Kajfasz, J. K., Abranches, J., & Lemos, J. A. C. (2011) · Microbiology · doi:10.1099/mic.0.052407-0 · Cited by 32 · see citing works
Takahashi, I., & Asami, T. (2018) · Journal of Experimental Botany · doi:10.1093/jxb/ery126 · Cited by 32 · see citing works
Ju, Y., He, L., Zhou, Y., Yang, T., Sun, K., Song, R., Yang, Y., Li, C., Sang, Z., Bao, R., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01746 · Cited by 31 · see citing works
Sharifzadeh, S., Boersma, M. J., Kocaoglu, O., Shokri, A., Brown, C. L., Shirley, J. D., Winkler, M. E., & Carlson, E. E. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00614 · Cited by 30 · see citing works
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Orth, R., Böttcher, T., & Sieber, S. A. (2010) · Chemical Communications · doi:10.1039/c0cc02825h · Cited by 30 · see citing works
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Elsholz, A. K. W., Gerth, U., & Hecker, M. (2010) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/b978-0-12-381045-8.00003-5 · Cited by 29 · see citing works
Chemistry-based functional proteomics for drug target deconvolution
Wang, K., Yang, T., Wu, Q., Zhao, X., Nice, E. C., & Huang, C. (2012) · Expert Review of Proteomics · doi:10.1586/epr.12.19 · Cited by 29 · see citing works
Kannappan, A., Ramanathan, S., Nivetha, A., Annapoorani, A., Pandian, S. K., & Ravi, A. V. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-019-09941-6 · Cited by 28 · see citing works
Kunzmann, M. H., Bach, N. C., Bauer, B., & Sieber, S. A. (2013) · Chemical Science · doi:10.1039/c3sc52228h · Cited by 28 · see citing works
Self-citationJing, S., Ren, X., Wang, L., Kong, X., Wang, X., Chang, X., Guo, X., Shi, Y., Guan, J., Wang, T., et al. (2022) · Virulence · doi:10.1080/21505594.2022.2051313 · Cited by 27 · see citing works
Protein Reactivity of Natural Product-Derived γ-Butyrolactones
Kunzmann, M. H., Staub, I., Böttcher, T., & Sieber, S. A. (2010) · Biochemistry · doi:10.1021/bi101858g · Cited by 27 · see citing works
Self-citationHindered Brønsted bases as Lewis base catalysts
Tabassum, S., Sereda, O., Reddy, P. V. G., & Wilhelm, R. (2009) · Organic & Biomolecular Chemistry · doi:10.1039/b908899g · Cited by 26 · see citing works
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Stahl, M. M. S., & Sieber, S. A. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.08.007 · Cited by 26 · see citing works
Self-citationMalik, I. T., Pereira, R., Vielberg, M.-T., Mayer, C., Straetener, J., Thomy, D., Famulla, K., Castro, H. C., Saß, P., Groll, M., et al. (2020) · ChemBioChem · doi:10.1002/cbic.201900787 · Cited by 25 · see citing works
A Concise Total Synthesis of (±)‐Vibralactone
Nistanaki, S. K., Boralsky, L. A., Pan, R. D., & Nelson, H. M. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201812711 · Cited by 24 · see citing works
- Authors
- Böttcher, T., & Sieber, S. A.
- Affiliations
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Sieber, Stephan A.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-10-11
- Volume
- 130
- Issue
- 44
- Pages
- 14400-14401
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2026902916
- Cited by
- 207
- References
- 14
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 9 · 2023: 12 · 2022: 8 · 2021: 6 · 2020: 17 · 2019: 14 · 2018: 15 · 2017: 14 · 2016: 10 · 2015: 6 · 2014: 8 · 2013: 21 · 2012: 11
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- β-lactones, ClpP protease, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, virulence factor inhibition, hemolysin, proteolytic enzymes, lipase, DNase, multidrug resistance, chemoproteomics, cell-permeable inhibitors, antibiotic alternatives
- MeSH terms
- Lactones, Staphylococcus aureus, Substrate Specificity, Serine Proteinase Inhibitors, Virulence Factors, Endopeptidase Clp, Methicillin-Resistant Staphylococcus aureus
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