Evaluation of silibinin as an efflux pump inhibitor in Bacillus subtilis

Yıl 2021, Cilt: 8 Sayı: 2, 104 - 112, 15.06.2021

Fatma Altınışık Başak Ataş Fatma Gizem Avcı

https://doi.org/10.21448/ijsm.865031

Cited By: 1

Öz

Antibiotic resistance has become a global health problem for humankind. Improper use of antibiotics resulted in the increasing evolved bacterial resistance to them. There are different types of bacterial resistance mechanisms including efflux pumps. To overcome the efflux pump activity on the drugs, combinatorial therapy of the existing antimicrobials with natural products is a promising insight to prevent increasing multidrug resistance. In this study, the inhibitory action of a plant-derived molecule silibinin on efflux pumps of Bacillus subtilis was investigated. The cellular effect of silibinin was investigated using minimum inhibitory concentration and growth studies. In addition, the efflux pump action of silibinin was monitored by ethidium bromide accumulation assay on the organism. According to results, silibinin has a MIC value between 100-200 µgmL-1 on microplate assay and 100 µgmL-1 of silibinin inhibited the cell growth. Ethidium bromide accumulation assays were performed at a safe silibinin range (25 and 50 µgmL-1) for eliminating the cell death, and ethidium bromide accumulation was increased with the increasing silibinin concentration. Ethidium bromide accumulation and growth results proved that silibinin has significant efflux pump inhibitor activity on Bacillus subtilis cells and silibinin is a promising inhibitor candidate to eliminate bacterial resistance mechanism.

Anahtar Kelimeler

Silibinin, efflux pump inhibitor, Bacillus subtilis, multidrug resistance

Kaynakça

• Amsterdam, D. (1997). Susceptibility testing of antimicrobials in liquid media. In V. Loman (Ed.), Antibiotics in laboratory medicine (pp. 51–111). Maple Press.
• Ahmed, M., Lyass, L., Markham, P. N., Taylor, S. S., Vazquez-Laslop, N., Neyfakh, A. A. (1995). Two highly similar multidrug transporters of Bacillus subtilis whose expression is differentially regulated. J. Bacteriol., 177(14), 3904 3910. https://doi.org/10.1128/jb.177.14.3904-3910.1995
• Avci, F. G., Atas, B., Aksoy, C. S., Kurpejovic, E., Toplan, G. G., Gurer, C., Guillerminet, M., Orelle, C., Jault, J.M., Akbulut Sariyar, B. (2019). Repurposing bioactive aporphine alkaloids as efflux pump inhibitors. Fitoterapia, 139, 104371. https://doi.org/10.1016/j.fitote.2019.104371
• Baranova, N. N., Danchin, A., Neyfakh, A. A. (1999). Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux transporters. Mol. Microbiol., 31(5), 1549–1559. https://doi.org/10.1046/j.1365-2958.1999.01301.x
• Cai, J. Y., Wang, Y. Y., Ma, K., Hou, Y. N., Li, J., Yao, G. D., Liu, W. W., Otkur, W., Hayashi, T., Itoh, K., Tashiro, S. I., Ikejima, T. (2017). Silibinin protects Staphylococcus aureus from UVC-induced bactericide via enhanced generation of reactive oxygen species. R.S.C. Adv., 7(53), 33194–33200. https://doi.org/10.1039/c7ra03981f
• Chan, B. C. L., Ip, M., Lau, C. B. S., Lui, S. L., Jolivalt, C., Ganem-Elbaz, C., Litaudon, M., Reiner, N. E., Gong, H., See, R. H., Fung, K. P., Leung, P. C. (2011). Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase. J. Ethnopharmacol., 137(1), 767–773. https://doi.org/10.1016/j.jep.2011.06.039
• de Oliveira, D. R., Tintino, S. R., Braga, M. F. B. M., Boligon, A. A., Athayde, M. L., Coutinho, H. D. M., de Menezes, I. R. A., Fachinetto, R. (2015). In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin. Bio.Med. Res. Int., 292797. https://doi.org/10.1155/2015/292797
• Dobiasová, S., Řehořová, K., Kučerová, D., Biedermann, D., Káňová, K., Petrásková, L., Koucká, K., Václavíková, R., Valentová, K., Ruml, T., Macek, T., Křen, V., Viktorová, J. (2020). Multidrug resistance modulation activity of silybin derivatives and their anti-inflammatory potential. Antioxidants, 9(5), 455. https://doi.org/10.3390/antiox9050455
• Du, D., van Veen, H. W., Murakami, S., Pos, K. M., Luisi, B. F. (2015). Structure, mechanism and cooperation of bacterial multidrug transporters. Curr. Opin. Struct. Biol., 33, 76–91. https://doi.org/10.1016/j.sbi.2015.07.015
• Gibbons, S., Moser, E., Kaatz, G. W. (2004). Catechin gallates inhibit multidrug resistance (MDR) in Staphylococcus aureus. Planta Med., 70(12), 1240 1242. https://doi.org/10.1055/s-2004-835860
• Gibbons, S., Oluwatuyi, M., Kaatz, G. W. (2003). A novel inhibitor of multidrug efflux pumps in Staphylococcus aureus. J. Antimicrob. Chemother., 51, 13 17. https://doi.org/10.1093/jac/dkg044
• Jin, G., Zhang, J., Guo, N., Feng, H., Li, L., Liang, J., Sun, K., Wu, X., Wang, X., Liu, M., Deng, X., Yu, L. (2011). The plant alkaloid piperine as a potential inhibitor of ethidium bromide efflux in Mycobacterium smegmatis. J. Med. Microbiol., 60(2), 223–229. https://doi.org/10.1099/jmm.0.025734-0
• Kumar, A., Khan, I. A., Koul, S., Koul, J. L., Taneja, S. C., Ali, I., Ali, F., Sharma, S., Mirza, Z. M., Kumar, M., Sangwan, P. L., Gupta, P., Thota, N., Qazi, G. N. (2008). Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J. Antimicrob. Chemother., 61, 1270–1276. https://doi.org/10.1093/jac/dkn088
• Lamut, A., Peterlin Mašič, L., Kikelj, D., Tomašič, T. (2019). Efflux pump inhibitors of clinically relevant multidrug resistant bacteria. Med. Res. Rev., 39(6), 2460–2504. https://doi.org/10.1002/med.21591
• Lorca, G. L., Barabote, R. D., Zlotopolski, V., Tran, C., Winnen, B., Hvorup, R. N., Stonestrom, A. J., Nguyen, E., Huang, L. W., Kim, D. S., Saier, M. H. (2007). Transport capabilities of eleven gram-positive bacteria: Comparative genomic analyses. Biochimi. Biophys. Acta, 1768(6), 1342–1366. https://doi.org/10.1016/j.bbamem.2007.02.007
• Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., Harbarth, S., Hindler, J. F., Kahlmeter, G., Olsson-Liljequist, B., Paterson, D. L., Rice, L. B., Stelling, J., Struelens, M. J., Vatopoulos, A., Weber, J. T., Monnet, D. L. (2012). Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect., 18(3), 268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x
• Mahmood, H. Y., Jamshidi, S., Sutton, J. M., Rahman, K. M. (2016). Current Advances in Developing Inhibitors of Bacterial Multidrug Efflux Pumps. Curr. Med. Chem., 23(10), 1062–1081. https://doi.org/10.2174/0929867323666160304150522
• Masaoka, Y., Ueno, Y., Morita, Y., Kuroda, T. (2000). A Two-Component Multidrug Efflux Pump, EbrAB, in Bacillus subtilis. J. Bacteriol., 182(8), 2307–2312. https://doi.org/10.1128/JB.182.8.2307-2310.2000
• Neyfakh, A. A., Bidnenko, V. E., Chen, L. B. (1991). Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. Proc. Natl. Acad. Sci. U.S.A., 88(11), 4781–4785. https://doi.org/10.1073/pnas.88.11.4781
• Schwarz, S., Chaslus-Dancla, E. (2001). Use of antimicrobials in veterinary medicine and mechanisms of resistance. Vet. Res., 32(3 4), 201 225. https://doi.org/10.1051/vetres:2001120
• Serçinoğlu, O., Senturk, D., Altinisik Kaya, F. E., Avci, F. G., Frlan, R., Ozbek, P., Jault, J.M., Sariyar Akbulut, B. (2020). Identification of novel inhibitors of the ABC transporter BmrA. Bioorg. Chem., 105, 104452. https://doi.org/10.1016/j.bioorg.2020.104452
• Shen, X., Liu, H., Li, G., Deng, X., Wang, J. (2018). Silibinin attenuates Streptococcus suis serotype 2 virulence by targeting suilysin. J. Appl. Microbiol., 126(2), 435–442. https://doi.org/10.1111/jam.14149
• Steinfels, E., Orelle, C., Fantino, J.R., Dalmas, O., Rigaud, J. L., Denizot, F., Di Pietro, A., Jault, J. M. (2004). Characterization of YvcC (BmrA), a Multidrug ABC Transporter Constitutively Expressed in Bacillus subtilis. Biochemistry, 43(23), 7491–7502. https://doi.org/10.1021/bi0362018
• Stermitz, F. R., Lorenz, P., Tawara, J. N., Zenewicz, L. A., Lewis, K. (2000). Synergy in a medicinal plant: Antimicrobial action of berberine potentiated by 5’-methoxyhydnocarpin, a multidrug pump inhibitor. Proc. Natl. Acad. Sci. U.S.A., 97(4), 1433-1437. https://doi.org/10.1073/pnas.030540597
• Tsuge, K., Ohata, Y., Shoda, M. (2001). Gene yerP, involved in surfactin self-resistance in Bacillus subtilis. Antimicrob. Agents Chemother., 45(12), 3566–3573. https://doi.org/10.1128/AAC.45.12.3566-3573.2001
• Van Duijkeren, E., Schink, A. K., Roberts, M. C., Wang, Y., Schwarz, S. (2018). Mechanisms of bacterial resistance to antimicrobial agents. In S. Schwarz, L. Cavaco, J. Shen (Ed.), Antimicrobial Resistance in Bacteria from Livestock and Companion Animals (pp. 51-82). Washington: ASM Press. https://doi.org/10.1128/microbiolspec.arba-0019-2017
• Wang, D., Xie, K., Zou, D., Meng, M., Xie, M. (2018). Inhibitory effects of silybin on the efflux pump of methicillin-resistant Staphylococcus aureus. Mol. Med. Rep., 18(1), 827-833. https://doi.org/10.3892/mmr.2018.9021
• Wlcek, K., Koller, F., Ferenci, P., Stieger, B. (2013). Hepatocellular organic anion-transporting polypeptides (OATPs) and multidrug resistance-associated protein 2 (MRP2) are inhibited by silibinin. Drug Metab. Dispos., 41(8), 1522 1528. https://doi.org/10.1124/dmd.113.051037
• Woolridge, D. P., Vazquez-Laslop, N., Markham, P. N., Chevalier, M. S., Gerner, E. W., Neyfakh, A. A. (1997). Efflux of the Natural Polyamine Spermidine Facilitated by the Bacillus subtilis Multidrug Transporter Blt. J. Biol. Chem., 272(14), 8864–8866. https://doi.org/10.1074/jbc.272.14.8864
• Zhou, S., Lim, L. Y., Chowbay, B. (2004). Herbal Modulation of P-Glycoprotein. Drug Metab. Rev., 36(1), 57-104. https://doi.org/10.1081/DMR-120028427