Combination of Acacetin with Antibiotics against Methicillin Resistant Staphylococcus aureus Isolated from Clinical Specimens

Jeong-Dan Cha, Sung-Mi Choi, Jeong Hye Park

Department of Dental Hygiene, Daegu Health College, Daegu, South Korea.
Department of Nursing, Dong-eui University, Bu-san, South Korea.
Department of Research Development, Institute of Jinan Red Ginseng, Jinan, South Korea.

DOI: 10.4236/abb.2014.54048                

Abstract

Methicillin-restitant Staphylococcus aureus (MRSA) is very dangerous bacteria and one of the most feared nosocomial germs. In this study, acacetin was evaluated against 20 clinical isolates of MRSA, either alone or in combination with antibiotics. The acacetin exhibited a good activity against isolates MRSA with MICs/MBCs ranged between 10-80/20-160 μg/mL, for ampicillin 64-1024/128-2048 μg/mL, and for oxacillin 8-32/16-64 μg/mL. The combination of acacetin plus oxacillin or ampicillin was reduced by ≥4-fold against isolates MRSA tested, evidencing a synergistic effect as defined by a FICI of ≤0.5. Furthermore, a time-kill study evaluating the growth of the tested bacteria was completely attenuated after 2-5 h of treatment with the 1/2 MIC of acacetin, regardless of whether it was administered alone or with oxacillin (1/2 MIC) or ampicillin (1/2 MIC). In conclusion, acacetin exerted synergistic effects when administered with oxacillin or ampicillin and the antibacterial activity and resistant regulation of acacetin against clinical isolates of MRSA might be useful in controlling MRSA infections.

Keywords

Acacetin; Methicillin-Resistant Staphylococcus aureus; Minimum Inhibitory Concentrations; Minimum Bactericidal Concentrations; Time-Kill Curves; Fractional Inhibitory Concentration

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Stefani, S. and Varaldo, P.E. (2003) Epidemiology of Methicillin Resistant Staphylococci in Europe. Clinical Microbiology and Infection, 9, 1179-1186. http://dx.doi.org/10.1111/j.1469-0691.2003.00698.x
[2]	Pourakbari, B., Rezaizadeh, G., Mahmoudi, S. and Mamishi, S. (2012) Epidemiology of Nosocomial Infections in Pediatric Patients in an Iranian Referral Hospital. Journal of Preventive Medicine and Hygiene, 53, 204-206.
[3]	Krishna, S. and Miller, L.S. (2012) Host-Pathogen Interactions between the Skin and Staphylococcus aureus. Current Opinion in Microbiology, 15, 28-35. http://dx.doi.org/10.1016/j.mib.2011.11.003
[4]	Cleven, B.E., Palka-Santini, M., Gielen, J., Meembor, S., Kronke, M. and Krut, O. (2006) Identification and Characterization of Bacterial Pathogens Causing Bloodstream Infections by DNA Microarray. Journal of Clinical Microbiology, 44, 2389-2397. http://dx.doi.org/10.1128/JCM.02291-05
[5]	Zecconi, A. and Scali, F. (2013) Staphylococcus aureus Virulence Factors in Evasion from Innate Immune Defenses in Human and Animal Diseases. Immunology Letters, 150, 12-22. http://dx.doi.org/10.1016/j.imlet.2013.01.004
[6]	Thati, V., Shivannavar, C.T. and Gaddad, S.M. (2011) Vancomycin Resistance among Methicillin Resistant Staphylococcus aureus Isolates from Intensive Care Units of Tertiary Care Hospitals in Hyderabad. The Indian Journal of Medical Research, 134, 704-708. http://dx.doi.org/10.4103/0971-5916.91001
[7]	Périchon, B. and Courvalin, P. (2006) Synersism between Beta-Lactams and Glycopeptides against VanA-Type Methicillin-Resistant Staphylococcus aureus and Heterologous Expression of the vanA Operon. Antimicrobial Agents and Chemotherapy, 50, 3622-3630. http://dx.doi.org/10.1128/AAC.00410-06
[8]	Dahiya, P. and Purkayastha, S. (2012) Phytochemica Screening and Antimicrobial Activity of Some Medicinal Plant Multi-Drug Resistant Bacteria from Clinical Isolates. Indian Journal of Pharmaceutical Sciences, 74, 443-450. http://dx.doi.org/10.4103/0250-474X.108420
[9]	Su, X., Howell, A.B. and D’Souza, D.H. (2012) Antibacterial Effects of Plant-Derived Extracts on Methicillin-Resistant Staphylococcus aureus. Foodborne Pathogens and Disease, 9, 573-578. http://dx.doi.org/10.1089/fpd.2011.1046
[10]	Sasaki, H., Kashiwada, Y., Shibata, H. and Takaishi, Y. (2012) Prenylated Flavonoids from Desmodium caudatum and Evaluation of Their Anti-MRSA Activity. Phytochemistry, 82, 136-142. http://dx.doi.org/10.1016/j.phytochem.2012.06.007
[11]	Rasul, A., Millimouno, F.M., Ali Eltayb, W., Ali, M., Li, J. and Li, X. (2013) Pinocembrin: A Novel Natural Compound with Versatile Pharmacological and Biological Activities. BioMed Research International, 2013, Article ID: 379850. http://dx.doi.org/10.1155/2013/379850
[12]	Chirumbolo, S. (2010) The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function. Inflammation Allergy Drug Targets, 9, 263-285.
[13]	Czaplińska, M., Czepas, J. and Gwozdziński, K. (2012) Structure, Antioxidative and Anticancer Properties of Flavonoids. Postepy Biochemii, 58, 235-244.
[14]	Fong, Y., Shen, K.H., Chiang, T.A. and Shih, Y.W. (2010) Acacetin Inhibits TPA-Induced MMP-2 and u-PA Expressions of Human Lung Cancer Cells through Inactivating JNK Signaling Pathway and Reducing Binding Activities of NF-kappaB and AP-1. Journal of Food Science, 75, 1750-3841. http://dx.doi.org/10.1111/j.1750-3841.2009.01438.x
[15]	Ha, S.K., Moon, E., Lee, P., Ryu, J.H., Oh, M.S. and Kim, S.Y. (2012) Acacetin Attenuates Neuroinflammation via Regulation the Response to LPS Stimuli in Vitro and in Vivo. Neurochemical Research, 37, 1560-1567. http://dx.doi.org/10.1007/s11064-012-0751-z
[16]	da Cunha, M.G., Franchin, M., de Carvalho Galvao, L.C., de Ruiz, A.L., de Carvalho, J.E., Ikegaki, M., de Alencar, S.M., Koo, H. and Rosalen, P.L. (2013) Antimicrobial and Antiproliferative Activities of Stingless Bee Melipona scutellaris Geopropolis. BMC Complementary & Alternative Medicine, 28, 23. http://dx.doi.org/10.1186/1472-6882-13-23
[17]	Qin, R., Xiao, K., Li, B., Jiang, W., Peng, W., Zheng, J. and Zhou, H. (2013) The Combination of Catechin and Epicatechin Gallate from Fructus Crataegi Potentiates Beta-Lactam Antibiotics against Methicillin-Resistant Staphylococcus aureus (MRSA) in Vitro and in Vivo. International Journal of Molecular Sciences, 14, 1802-1821. http://dx.doi.org/10.3390/ijms14011802
[18]	Wallet, F., Roussel-Delvallez, M. and Courcol, R.J. (1996) Choice of a Routine Method for Detecting Methicillin-Resistance in Staphylococci. The Journal of Antimicrobial Chemotherapy, 37, 901-909. http://dx.doi.org/10.1093/jac/37.5.901
[19]	Cha, J.D., Jeong, M.R., Jeong, S.I. and Lee, K.Y. (2007) Antibacterial Activity of Sophoraflavanone G Isolated from the Roots of Sophora flavescens. Journal of Microbiology and Biotechnology, 17, 858-864.
[20]	Climo, M.W., Patron, R.L. and Archer, G.L. (1999) Combinations of Vancomycin and Beta-Lactams Are Synergistic against Staphylococci with Reduced Susceptibilities to Vancomycin. Antimicrobial Agents and Chemotherapy, 43, 1747-1753.
[21]	Gibbons, S., Leimkugel, J., Oluwatuyi, M. and Heinrich, M. (2003) Activity of Zanthoxylum clava-herculis Extracts against Multi-Drug Resistant Methicillin-Resistant Staphylococcus aureus (mdr-MRSA). Phytotherapy Research, 17, 274-275. http://dx.doi.org/10.1002/ptr.1112
[22]	Kitahara, T., Aoyama, Y., Hirakata, Y., Kamihira, S., Kohno, S., Ichikawa, N., Nakashima, M., Sasaki, H. and Higuchi, S. (2006) In Vitro Activity of Lauric Acid or Myristylamine in Combination with Six Antimicrobial Agents against Methicillin-Resistant Staphylococcus aureus (MRSA). International Journal of Antimicrobial Agents, 27, 51-57. http://dx.doi.org/10.1016/j.ijantimicag.2005.08.020
[23]	Sato, Y., Suzakim S., Nishikawa, T., Kihara, M., Shibata, H. and Higuti, T. (2000) Phytochemical Flavones Isolated from Scutellaria barbata and Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus. Journal of Ethnopharmacology, 72, 484-488. http://dx.doi.org/10.1016/S0378-8741(00)00265-8
[24]	Cushnie, T.P. and Lamb, A.J. (2005) Antimicrobial Activity of Flavonoids. International Journal of Antimicrobial Agents, 26, 343-356. http://dx.doi.org/10.1016/j.ijantimicag.2005.09.002
[25]	Yi, S.M., Zhu, J.L., Fu, L.L. and Li, J.R. (2010) Tea Polyphenols Inhibit Pseudomonas aeruginosa through Damage to the Cell Membrane. International Journal of Food Microbiology, 144, 111-117. http://dx.doi.org/10.1016/j.ijfoodmicro.2010.09.005
[26]	Yi, S., Wang, W., Bai, F., Zhu, J., Li, J., Li, X., Xu, Y., Sun, T. and He, Y. (2013) Antimicrobial Effect and Membrane-Active Mechanism of Tea Polyphenols against Serratia marcescens. World Journal of Microbiology & Biotechnology, 27.
[27]	Holler, J.G., Slotved, H.C., Mølgaard, P., Olsen, C.E. and Christensen, S.B. (2012) Chalcone Inhibitors of the NorA Efflux Pump in Staphylococcus aureus Whole Cells and Enriched Everted Membrane Vesicles. Bioorganic & Medicinal Chemistry, 20, 4514-4521. http://dx.doi.org/10.1016/j.bmc.2012.05.025
[28]	Roselli, M., Britti, M.S., Le Huërou-Luron, I., Marfaing, H., Zhu, W.Y. and Mengheri, E. (2007) Effect of Different Plant Extracts and Natural Substances (PENS) against Membrane Damage Induced by Enterotoxigenic Escherichia coli K88 in Pig Interstinal Cells. Toxicology in Vitro, 21, 224-229. http://dx.doi.org/10.1016/j.tiv.2006.09.012
[29]	Liu, X.L., Zhang, X.J., Fu, Y.J., Zu, Y.G., Wu, N., Liang, L. and Efferth, T. (2011) Cajanol Inhibits the Growth of Escherichia coli and Staphylococcus aureus by Acting on Membrane and DNA Damage. Planta Medica, 77, 158-163. http://dx.doi.org/10.1055/s-0030-1250146