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Food Microbiology and Biotechnology (FMB) | Bioactive compounds and Physiological properties
Madurahydroxylactone, an Inhibitor of Staphylococcus aureus FtsZ from Nonomuraea sp. AN100570
1Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 34141, Republic of Korea, 2College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea, 3Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133002, P.R. China
Received: August 18, 2017; Accepted: September 6, 2017
J. Microbiol. Biotechnol. 2017; 27(11): 1994-1998
Published November 28, 2017 https://doi.org/10.4014/jmb.1708.08044
Copyright © The Korean Society for Microbiology and Biotechnology.
Abstract
FtsZ, a bacterial cell-division protein, is an attractive antibacterial target. In the screening for
an inhibitor of Staphylococcus aureus FtsZ, madurahydroxylactone (1) and its related
derivatives 2-5 were isolated from Nonomuraea sp. AN100570. Compound 1 inhibited S. aureus
FtsZ with an IC50 of 53.4 μM and showed potent antibacterial activity against S. aureus and
MRSA with an MIC of 1 μg/ml, whereas 2-5 were weak or inactive. Importantly, 1 induced
cell elongation in the cell division phenotype assay, whereas 2-5 did not. It indicates that 1
exhibits its potent antibacterial activity via inhibition of FtsZ, and the hydroxyl group and
hydroxylactone ring of 1 are critical for the activity. Thus, madurahydroxylactone is a new
type of inhibitor of FtsZ.
Keywords
Madurahydroxylactone, FtsZ, inhibitor, Nonomuraea, antibacterial
References
- Klein E, Smith DL, Laxminarayan R. 2007. Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005. Emerg. Infect. Dis 13: 1840-1846.
- Levy SB, Marshall B. 2004. Antibacterial resistance worldwide:causes, challenges and responses. Nat. Med. 10: S122-S129.
- Brown ED, Wright GD. 2016. Antibacterial drug discovery in the resistance era. Nature 529: 336-343.
- Butler MS, Cooper MA. 2012. Screening strategies to identify new antibiotics. Curr. Drug Targets 13: 373-387.
- Lock RL, Harry EJ. 2008. Cell-division inhibitors: new insights for future antibiotics. Nat. Rev. Drug Discov. 7: 324-338.
- Vollmer W. 2006. The prokaryotic cytoskeleton: a putative target for inhibitors and antibiotic s? Appl. Microbiol. Biotechnol. 73: 37-47.
- Kapoor S, Panda D. 2009. Targeting FtsZ for antibacterial therapy: a promising avenue. Expert Opin. Ther. Targets 13: 1037-1051.
- Haydon DJ, Stokes NR, Ure R, Galbraith G, Bennett JM, Brown DR, et al. 2008. An inhibitor of FtsZ with potent and selective anti-staphylococcal activity. Science 321: 1673-1675.
- Sun N, Chan FY, Lu YJ, Neves MA, Lui HK, Wang Y et al. 2014. Rational design of berberine-based FtsZ inhibitors with broad-spectrum antibacterial activity. PLoS One 9: e97514.
- Wang J, Galgoci A, Kodali S, Herath KB, Jayasuriya H, Dorso K, et al. 2003. Discovery of a small molecule that inhibits cell division by blocking FtsZ, a novel therapeutic target of antibiotics. J. Biol. Chem 278: 44424-44428.
- Stokes NR, Sievers J, Barker S, Bennett JM, Brown DR, Collins I, et al. 2005. Novel inhibitors of bacterial cytokinesis identified by a cell-based antibiotic screening assay. J. Biol. Chem. 280: 39709-39715.
- Domadia PN, Bhunia A, Sivaraman J, Swarup S, Dasgupta D. 2008. Berberine targets assembly of Escherichia coli c ell division protein FtsZ. Biochemistry 47: 3225-3234.
- Beuria TK, Santra MK, Panda D. 2005. Sanguinarine blocks cytokinesis in bacteria by inhibiting FtsZ assembly and bundling. Biochemistry 44: 16584-16593.
- Park YS, Grove CI, Gonzalez-Lopez M, Urgaonkar S, Fettinger JC, Shaw JT. 2011. Synthesis of (-)-viriditoxin: a 6,6’-binaphthopyran-2-one that targets the bacterial cell division protein FtsZ. Angew. Chem. Int. Ed. Engl. 50: 3730-3733.
- Stokes NR, Baker N, Bennett JM, Berry J, Collins I, Czaplewski LG, et al. 2013. An improved small-molecule inhibitor of FtsZ with superior in vitro potency, drug-like properties, and in vivo efficacy. Antimicrob. Agents Chemother. 57: 317-325.
- Fleck WF, Strauss DG, Meyer J, Porstendorfer G. 1978. Fermentation, isolation, and biological activity of maduramycin:a new antibiotic from Actinomadura rubra. Z. Allg. Mikrobiol. 18: 389-398.
- Marchand C, Beutler JA, Wamiru A, Budihas S, Mollmann U, Heinisch L et al. 2008. Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H. Antimicrob. Agents Chemother. 52: 361-364.
- Heinisch L, Roemer E, Jutten P, Haas W, Werner W, Mollmann U. 1999. Semisynthetic derivatives of madura hydroxylactone and their antibacterial activities. J. Antibiot. (Tokyo) 52: 1029-1041.
- Strauss DG, Baum M, Fleck WF. 1986. Butylmaduramycin, a new antibiotic from Actinomadura rubra. J. Basic Microbiol. 26: 169-172.
- Zheng CJ, Sohn MJ, Kim WG. 2009. Vinaxanthone, a new FabI inhibitor from Penicillium sp. J. Antimicrob. Chemother. 63: 949-953.
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J. Microbiol. Biotechnol. 2017; 27(11): 1994-1998
Published online November 28, 2017 https://doi.org/10.4014/jmb.1708.08044
Copyright © The Korean Society for Microbiology and Biotechnology.
Madurahydroxylactone, an Inhibitor of Staphylococcus aureus FtsZ from Nonomuraea sp. AN100570
Bo-Min Kim 1, 2, Ha-Young Choi 1, Geon-Woo Kim 1, Chang-Ji Zheng 3, Young-Ho Kim 3 and Won-Gon Kim 1*
1Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 34141, Republic of Korea, 2College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea, 3Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji 133002, P.R. China
Received: August 18, 2017; Accepted: September 6, 2017
Abstract
FtsZ, a bacterial cell-division protein, is an attractive antibacterial target. In the screening for
an inhibitor of Staphylococcus aureus FtsZ, madurahydroxylactone (1) and its related
derivatives 2-5 were isolated from Nonomuraea sp. AN100570. Compound 1 inhibited S. aureus
FtsZ with an IC50 of 53.4 μM and showed potent antibacterial activity against S. aureus and
MRSA with an MIC of 1 μg/ml, whereas 2-5 were weak or inactive. Importantly, 1 induced
cell elongation in the cell division phenotype assay, whereas 2-5 did not. It indicates that 1
exhibits its potent antibacterial activity via inhibition of FtsZ, and the hydroxyl group and
hydroxylactone ring of 1 are critical for the activity. Thus, madurahydroxylactone is a new
type of inhibitor of FtsZ.
Keywords: Madurahydroxylactone, FtsZ, inhibitor, Nonomuraea, antibacterial
References
- Klein E, Smith DL, Laxminarayan R. 2007. Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005. Emerg. Infect. Dis 13: 1840-1846.
- Levy SB, Marshall B. 2004. Antibacterial resistance worldwide:causes, challenges and responses. Nat. Med. 10: S122-S129.
- Brown ED, Wright GD. 2016. Antibacterial drug discovery in the resistance era. Nature 529: 336-343.
- Butler MS, Cooper MA. 2012. Screening strategies to identify new antibiotics. Curr. Drug Targets 13: 373-387.
- Lock RL, Harry EJ. 2008. Cell-division inhibitors: new insights for future antibiotics. Nat. Rev. Drug Discov. 7: 324-338.
- Vollmer W. 2006. The prokaryotic cytoskeleton: a putative target for inhibitors and antibiotic s? Appl. Microbiol. Biotechnol. 73: 37-47.
- Kapoor S, Panda D. 2009. Targeting FtsZ for antibacterial therapy: a promising avenue. Expert Opin. Ther. Targets 13: 1037-1051.
- Haydon DJ, Stokes NR, Ure R, Galbraith G, Bennett JM, Brown DR, et al. 2008. An inhibitor of FtsZ with potent and selective anti-staphylococcal activity. Science 321: 1673-1675.
- Sun N, Chan FY, Lu YJ, Neves MA, Lui HK, Wang Y et al. 2014. Rational design of berberine-based FtsZ inhibitors with broad-spectrum antibacterial activity. PLoS One 9: e97514.
- Wang J, Galgoci A, Kodali S, Herath KB, Jayasuriya H, Dorso K, et al. 2003. Discovery of a small molecule that inhibits cell division by blocking FtsZ, a novel therapeutic target of antibiotics. J. Biol. Chem 278: 44424-44428.
- Stokes NR, Sievers J, Barker S, Bennett JM, Brown DR, Collins I, et al. 2005. Novel inhibitors of bacterial cytokinesis identified by a cell-based antibiotic screening assay. J. Biol. Chem. 280: 39709-39715.
- Domadia PN, Bhunia A, Sivaraman J, Swarup S, Dasgupta D. 2008. Berberine targets assembly of Escherichia coli c ell division protein FtsZ. Biochemistry 47: 3225-3234.
- Beuria TK, Santra MK, Panda D. 2005. Sanguinarine blocks cytokinesis in bacteria by inhibiting FtsZ assembly and bundling. Biochemistry 44: 16584-16593.
- Park YS, Grove CI, Gonzalez-Lopez M, Urgaonkar S, Fettinger JC, Shaw JT. 2011. Synthesis of (-)-viriditoxin: a 6,6’-binaphthopyran-2-one that targets the bacterial cell division protein FtsZ. Angew. Chem. Int. Ed. Engl. 50: 3730-3733.
- Stokes NR, Baker N, Bennett JM, Berry J, Collins I, Czaplewski LG, et al. 2013. An improved small-molecule inhibitor of FtsZ with superior in vitro potency, drug-like properties, and in vivo efficacy. Antimicrob. Agents Chemother. 57: 317-325.
- Fleck WF, Strauss DG, Meyer J, Porstendorfer G. 1978. Fermentation, isolation, and biological activity of maduramycin:a new antibiotic from Actinomadura rubra. Z. Allg. Mikrobiol. 18: 389-398.
- Marchand C, Beutler JA, Wamiru A, Budihas S, Mollmann U, Heinisch L et al. 2008. Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H. Antimicrob. Agents Chemother. 52: 361-364.
- Heinisch L, Roemer E, Jutten P, Haas W, Werner W, Mollmann U. 1999. Semisynthetic derivatives of madura hydroxylactone and their antibacterial activities. J. Antibiot. (Tokyo) 52: 1029-1041.
- Strauss DG, Baum M, Fleck WF. 1986. Butylmaduramycin, a new antibiotic from Actinomadura rubra. J. Basic Microbiol. 26: 169-172.
- Zheng CJ, Sohn MJ, Kim WG. 2009. Vinaxanthone, a new FabI inhibitor from Penicillium sp. J. Antimicrob. Chemother. 63: 949-953.
