Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum

Eberhardt D, Wendisch VF (2016)
BMC Microbiology 16(1): 235.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
Background Corynebacterium glutamicum is a well-studied bacterium which naturally overproduces glutamate when induced by an elicitor. Glutamate production is accompanied by decreased 2-oxoglutatate dehydrogenase activity. Elicitors of glutamate production by C. glutamicum analyzed to molecular detail target the cell envelope. Results Ciprofloxacin, an inhibitor of bacterial DNA gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum wild type with concomitant excretion of glutamate. Enzyme assays showed that 2-oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addition. Transcriptome analysis revealed that this inhibitor of DNA gyrase increased RNA levels of genes involved in DNA synthesis, repair and modification. Glutamate production triggered by ciprofloxacin led to glutamate titers of up to 37 ± 1 mM and a substrate specific glutamate yield of 0.13 g/g. Even in the absence of the putative glutamate exporter gene yggB, ciprofloxacin effectively triggered glutamate production. When C. glutamicum wild type was cultivated under nitrogen-limiting conditions, 2-oxoglutarate rather than glutamate was produced as consequence of exposure to ciprofloxacin. Recombinant C. glutamicum strains overproducing lysine, arginine, ornithine, and putrescine, respectively, secreted glutamate instead of the desired amino acid when exposed to ciprofloxacin. Conclusions Ciprofloxacin induced DNA synthesis and repair genes, reduced 2-oxoglutarate dehydrogenase activity and elicited glutamate production by C. glutamicum. Production of 2-oxoglutarate could be triggered by ciprofloxacin under nitrogen-limiting conditions.
Corynebacterium glutamicum Ciprofloxacin DNA gyrase Glutamate Ornithine Putrescine Arginine Lysine 2-oxoglutarate Overflow metabolism
BMC Microbiology
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Eberhardt D, Wendisch VF. Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum. BMC Microbiology. 2016;16(1): 235.
Eberhardt, D., & Wendisch, V. F. (2016). Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum. BMC Microbiology, 16(1), 235. doi:10.1186/s12866-016-0857-6
Eberhardt, D., and Wendisch, V. F. (2016). Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum. BMC Microbiology 16:235.
Eberhardt, D., & Wendisch, V.F., 2016. Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum. BMC Microbiology, 16(1): 235.
D. Eberhardt and V.F. Wendisch, “Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum”, BMC Microbiology, vol. 16, 2016, : 235.
Eberhardt, D., Wendisch, V.F.: Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum. BMC Microbiology. 16, : 235 (2016).
Eberhardt, Dorit, and Wendisch, Volker F. “Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum”. BMC Microbiology 16.1 (2016): 235.
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56 References

Daten bereitgestellt von Europe PubMed Central.

The SOS response regulates adaptive mutation.
McKenzie GJ, Harris RS, Lee PL, Rosenberg SM., Proc. Natl. Acad. Sci. U.S.A. 97(12), 2000
PMID: 10829077
Excretion of glutamate from Corynebacterium glutamicum triggered by amine surfactants.
Duperray F, Jezequel D, Ghazi A, Letellier L, Shechter E., Biochim. Biophys. Acta 1103(2), 1992
PMID: 1543710
Studies on transformation of Escherichia coli with plasmids.
Hanahan D., J. Mol. Biol. 166(4), 1983
PMID: 6345791
A Corynebacterium glutamicum gene encoding a two-domain protein similar to biotin carboxylases and biotin-carboxyl-carrier proteins.
Jager W, Peters-Wendisch PG, Kalinowski J, Puhler A., Arch. Microbiol. 166(2), 1996
PMID: 8772169
Requirement of de novo synthesis of the OdhI protein in penicillin-induced glutamate production by Corynebacterium glutamicum.
Kim J, Fukuda H, Hirasawa T, Nagahisa K, Nagai K, Wachi M, Shimizu H., Appl. Microbiol. Biotechnol. 86(3), 2009
PMID: 19956942
Relationship between the glutamate production and the activity of 2-oxoglutarate dehydrogenase in Brevibacterium lactofermentum.
Kawahara Y, Takahashi-Fuke K, Shimizu E, Nakamatsu T, Nakamori S., Biosci. Biotechnol. Biochem. 61(7), 1997
PMID: 9255973
The phosphate starvation stimulon of Corynebacterium glutamicum determined by DNA microarray analyses.
Ishige T, Krause M, Bott M, Wendisch VF, Sahm H., J. Bacteriol. 185(15), 2003
PMID: 12867461
Glutamate is excreted across the cytoplasmic membrane through the NCgl1221 channel of Corynebacterium glutamicum by passive diffusion.
Hashimoto K, Murata J, Konishi T, Yabe I, Nakamatsu T, Kawasaki H., Biosci. Biotechnol. Biochem. 76(7), 2012
PMID: 22785475
Amino acid production processes.
Ikeda M., Adv. Biochem. Eng. Biotechnol. 79(), 2003
PMID: 12523387
Genetic makeup of the Corynebacterium glutamicum LexA regulon deduced from comparative transcriptomics and in vitro DNA band shift assays.
Jochmann N, Kurze AK, Czaja LF, Brinkrolf K, Brune I, Huser AT, Hansmeier N, Puhler A, Borovok I, Tauch A., Microbiology (Reading, Engl.) 155(Pt 5), 2009
PMID: 19372162
Studies on the amino acid fermentation. Part 1. Production of L-glutamic acid by various microorganisms.
Kinoshita S, Udaka S, Shimono M., J. Gen. Appl. Microbiol. 50(6), 2004
PMID: 15965888
The protein encoded by NCgl1221 in Corynebacterium glutamicum functions as a mechanosensitive channel.
Hashimoto K, Nakamura K, Kuroda T, Yabe I, Nakamatsu T, Kawasaki H., Biosci. Biotechnol. Biochem. 74(12), 2010
PMID: 21150093
Isolation of the murI gene from Brevibacterium lactofermentum ATCC 13869 encoding D-glutamate racemase.
Malathi KC, Wachi M, Nagai K., FEMS Microbiol. Lett. 175(2), 1999
PMID: 10386367
Carrier-mediated glutamate secretion by Corynebacterium glutamicum under biotin limitation.
Gutmann M, Hoischen C, Kramer R., Biochim. Biophys. Acta 1112(1), 1992
PMID: 1358200
Corynebacterium glutamicum as a host for synthesis and export of D-Amino Acids.
Stabler N, Oikawa T, Bott M, Eggeling L., J. Bacteriol. 193(7), 2011
PMID: 21257776
DNA gyrase, topoisomerase IV, and the 4-quinolones.
Drlica K, Zhao X., Microbiol. Mol. Biol. Rev. 61(3), 1997
PMID: 9293187
Construction of a prophage-free variant of Corynebacterium glutamicum ATCC 13032 for use as a platform strain for basic research and industrial biotechnology.
Baumgart M, Unthan S, Ruckert C, Sivalingam J, Grunberger A, Kalinowski J, Bott M, Noack S, Frunzke J., Appl. Environ. Microbiol. 79(19), 2013
PMID: 23892752
Biotin protein ligase from Corynebacterium glutamicum: role for growth and L: -lysine production.
Peters-Wendisch P, Stansen KC, Gotker S, Wendisch VF., Appl. Microbiol. Biotechnol. 93(6), 2011
PMID: 22159614
Effect of odhA overexpression and odhA antisense RNA expression on Tween-40-triggered glutamate production by Corynebacterium glutamicum.
Kim J, Hirasawa T, Sato Y, Nagahisa K, Furusawa C, Shimizu H., Appl. Microbiol. Biotechnol. 81(6), 2008
PMID: 18923827
Glutamate efflux mediated by Corynebacterium glutamicum MscCG, Escherichia coli MscS, and their derivatives.
Becker M, Borngen K, Nomura T, Battle AR, Marin K, Martinac B, Kramer R., Biochim. Biophys. Acta 1828(4), 2013
PMID: 23313454
DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
Pommier Y, Leo E, Zhang H, Marchand C., Chem. Biol. 17(5), 2010
PMID: 20534341
The bacterial LexA transcriptional repressor.
Butala M, Zgur-Bertok D, Busby SJ., Cell. Mol. Life Sci. 66(1), 2009
PMID: 18726173
Characterization of citrate utilization in Corynebacterium glutamicum by transcriptome and proteome analysis.
Polen T, Schluesener D, Poetsch A, Bott M, Wendisch VF., FEMS Microbiol. Lett. 273(1), 2007
PMID: 17559405
Gene expression of Corynebacterium glutamicum in response to the conditions inducing glutamate overproduction.
Kataoka M, Hashimoto KI, Yoshida M, Nakamatsu T, Horinouchi S, Kawasaki H., Lett. Appl. Microbiol. 42(5), 2006
PMID: 16620205
Mechanism of action of the lexA gene product.
Brent R, Ptashne M., Proc. Natl. Acad. Sci. U.S.A. 78(7), 1981
PMID: 7027256
Pyruvate carboxylase from Corynebacterium glutamicum: characterization, expression and inactivation of the pyc gene.
Peters-Wendisch PG, Kreutzer C, Kalinowski J, Patek M, Sahm H, Eikmanns BJ., Microbiology (Reading, Engl.) 144 ( Pt 4)(), 1998
PMID: 9579065
Ornithine cyclodeaminase-based proline production by Corynebacterium glutamicum.
Jensen JV, Wendisch VF., Microb. Cell Fact. 12(), 2013
PMID: 23806148
Glutamate racemase is an endogenous DNA gyrase inhibitor.
Ashiuchi M, Kuwana E, Yamamoto T, Komatsu K, Soda K, Misono H., J. Biol. Chem. 277(42), 2002
PMID: 12213801
Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum.
Radmacher E, Stansen KC, Besra GS, Alderwick LJ, Maughan WN, Hollweg G, Sahm H, Wendisch VF, Eggeling L., Microbiology (Reading, Engl.) 151(Pt 5), 2005
PMID: 15870446
Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum.
Sato H, Orishimo K, Shirai T, Hirasawa T, Nagahisa K, Shimizu H, Wachi M., J. Biosci. Bioeng. 106(1), 2008
PMID: 18691531
The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol.
Belanger AE, Besra GS, Ford ME, Mikusova K, Belisle JT, Brennan PJ, Inamine JM., Proc. Natl. Acad. Sci. U.S.A. 93(21), 1996
PMID: 8876238
Disruption of genes for the enhanced biosynthesis of α-ketoglutarate in Corynebacterium glutamicum.
Jo JH, Seol HY, Lee YB, Kim MH, Hyun HH, Lee HH., Can. J. Microbiol. 58(3), 2012
PMID: 22356563


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