A New Coumarin Compound DCH Combats Methicillin-resistant Biofilm by Targeting Arginine Repressor

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Aug 25

PMID 32832655

Citations 27

Authors

Di Qu

Zheng Hou

Jing Li

Liyang Luo

Shan Su

Zichen Ye

Yinlan Bai

Xinlei Zhang

Guanghui Chen

Zhoupeng Li

Yikun Wang

Xiaoyan Xue

Xiaoxing Luo

Mingkai Li

Affiliations

Soon will be listed here.

Abstract

infection is difficult to eradicate because of biofilm formation and antibiotic resistance. The increasing prevalence of methicillin-resistant (MRSA) infection necessitates the development of a new agent against bacterial biofilms. We report a new coumarin compound, termed DCH, that effectively combats MRSA in vitro and in vivo and exhibits potent antibiofilm activity without detectable resistance. Cellular proteome analysis suggests that the molecular mechanism of action of DCH involves the arginine catabolic pathway. Using molecular docking and binding affinity assays of DCH, and comparison of the properties of wild-type and ArgR-deficient MRSA strains, we demonstrate that the arginine repressor ArgR, an essential regulator of the arginine catabolic pathway, is the target of DCH. These findings indicate that DCH is a promising lead compound and validate bacterial ArgR as a potential target in the development of new drugs against MRSA biofilms.

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References

Lee J, Sperandio V, Frantz D, Longgood J, Camilli A, Phillips M . An alternative polyamine biosynthetic pathway is widespread in bacteria and essential for biofilm formation in Vibrio cholerae. J Biol Chem. 2009; 284(15):9899-907. PMC: 2665113. DOI: 10.1074/jbc.M900110200. View

Cardile A, Woodbury R, Sanchez Jr C, Becerra S, Garcia R, Mende K . Activity of Norspermidine on Bacterial Biofilms of Multidrug-Resistant Clinical Isolates Associated with Persistent Extremity Wound Infections. Adv Exp Med Biol. 2016; 973:53-70. PMC: 5438303. DOI: 10.1007/5584_2016_93. View

Guillemin M, Miles H, McDonald M . Activity of coumermycin against clinical isolates of staphylococci. Antimicrob Agents Chemother. 1986; 29(4):608-10. PMC: 180451. DOI: 10.1128/AAC.29.4.608. View

Van Duyne G, Ghosh G, Maas W, SIGLER P . Structure of the oligomerization and L-arginine binding domain of the arginine repressor of Escherichia coli. J Mol Biol. 1996; 256(2):377-91. DOI: 10.1006/jmbi.1996.0093. View

Roope L, Smith R, Pouwels K, Buchanan J, Abel L, Eibich P . The challenge of antimicrobial resistance: What economics can contribute. Science. 2019; 364(6435). DOI: 10.1126/science.aau4679. View

Abraham W . Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections. Antibiotics (Basel). 2016; 5(1). PMC: 4810405. DOI: 10.3390/antibiotics5010003. View

Bunter J, Seth-Smith H, Ruegg S, Heikinheimo A, Borel N, Johler S . Wild type agr-negative livestock-associated MRSA exhibits high adhesive capacity to human and porcine cells. Res Microbiol. 2016; 168(2):130-138. DOI: 10.1016/j.resmic.2016.09.006. View

Olsen I . Biofilm-specific antibiotic tolerance and resistance. Eur J Clin Microbiol Infect Dis. 2015; 34(5):877-86. DOI: 10.1007/s10096-015-2323-z. View

Allen A, Dupont C, Obornik M, Horak A, Nunes-Nesi A, McCrow J . Evolution and metabolic significance of the urea cycle in photosynthetic diatoms. Nature. 2011; 473(7346):203-7. DOI: 10.1038/nature10074. View

10.

Verhoef T, Redekop W, Daly A, van Schie R, de Boer A, der Zee A . Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. Br J Clin Pharmacol. 2013; 77(4):626-41. PMC: 3971980. DOI: 10.1111/bcp.12220. View

11.

Blaser M . Antibiotic use and its consequences for the normal microbiome. Science. 2016; 352(6285):544-5. PMC: 4939477. DOI: 10.1126/science.aad9358. View

12.

Xiong L, Teng J, Watt R, Kan B, Lau S, Woo P . Arginine deiminase pathway is far more important than urease for acid resistance and intracellular survival in Laribacter hongkongensis: a possible result of arc gene cassette duplication. BMC Microbiol. 2014; 14:42. PMC: 3936950. DOI: 10.1186/1471-2180-14-42. View

13.

Zapotoczna M, ONeill E, OGara J . Untangling the Diverse and Redundant Mechanisms of Staphylococcus aureus Biofilm Formation. PLoS Pathog. 2016; 12(7):e1005671. PMC: 4956047. DOI: 10.1371/journal.ppat.1005671. View

14.

Zhang H, Liu Y, Nie X, Liu L, Hua Q, Zhao G . The cyanobacterial ornithine-ammonia cycle involves an arginine dihydrolase. Nat Chem Biol. 2018; 14(6):575-581. DOI: 10.1038/s41589-018-0038-z. View

15.

Le K, Park M, Otto M . Immune Evasion Mechanisms of Biofilm Infection. Front Microbiol. 2018; 9:359. PMC: 5835508. DOI: 10.3389/fmicb.2018.00359. View

16.

Hobley L, Li B, Wood J, Kim S, Naidoo J, Ferreira A . Spermidine promotes biofilm formation by activating expression of the matrix regulator . J Biol Chem. 2017; 292(29):12041-12053. PMC: 5519356. DOI: 10.1074/jbc.M117.789644. View

17.

Vuong C, Kocianova S, Yao Y, Carmody A, Otto M . Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J Infect Dis. 2004; 190(8):1498-505. DOI: 10.1086/424487. View

18.

Ishii K, Tabuchi F, Matsuo M, Tatsuno K, Sato T, Okazaki M . Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis. Sci Rep. 2015; 5:17092. PMC: 4658547. DOI: 10.1038/srep17092. View

19.

Li M, Li J, Liu B, Zhou Y, Li X, Xue X . Synthesis, crystal structures, and anti-drug-resistant Staphylococcus aureus activities of novel 4-hydroxycoumarin derivatives. Eur J Pharmacol. 2013; 721(1-3):151-7. DOI: 10.1016/j.ejphar.2013.09.040. View

20.

Balaban N, Cirioni O, Giacometti A, Ghiselli R, Braunstein J, Silvestri C . Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP. Antimicrob Agents Chemother. 2007; 51(6):2226-9. PMC: 1891383. DOI: 10.1128/AAC.01097-06. View