Screening of Indian medicinal plants as efflux pump inhibitors of fluoroquinolones

Efflux mechanisms have become broadly recognized as major components of resistance to many classes of antibiotics. Efflux related multidrug resistance (MDR) is a significant means by which bacteria can evade the effects of antibacterial agents. This study sought to give a scientific basis to plants already used for traditional purposes as bacterial efflux pump inhibitors (EPIs). A decline in minimum inhibitory concentration (MIC) 1/2 to 1/8 was used to determine the activity of 35 Indian medicinal plant extracts as drug EPIs against various bacterial strains. Fluoroquinolones (ciprofloxacin and ofloxacin) possesses antibacterial activity and when combined with plant extracts resulted in synergistic interactions by declining its MIC to 1/2 in 10 plants and 1/4 in 6 plants. Methanolic extracts of twelve plants were found to be putative EPI hence, the compounds in these extracts can serve as templates of new antibacterial agents. Plant extracts significantly enhanced accumulation and decreased the efflux of fluoroquinolones in bacterial strains, suggesting their ability to inhibit bacterial efflux pumps. EPI reduced the ciprofloxacin and ofloxacin MIC by 1/4 in 3 and 1 strains respectively. Our data support the fact that increased fluoroquinolones usage can negatively impact susceptibility of bacterial strains. Plants should be further exploited for their potential to produce compounds capable of blocking the mechanism of efflux.

[1]  S. Voravuthikunchai,et al.  Thai ethnomedicinal plants as resistant modifying agents for combating Acinetobacter baumannii infections , 2012, BMC Complementary and Alternative Medicine.

[2]  Pooja Bharti,et al.  43. Antibacterial activity and Chemical Composition of Essential Oils of Ten Aromatic Plants against selected Bacteria , 2012 .

[3]  S. Mukanganyama,et al.  In Vitro Antibacterial Activity of Selected Medicinal Plants from Zimbabwe , 2011 .

[4]  M. M. Rahman,et al.  Natural and synthetic compounds such as trimethoprim behave as inhibitors of efflux in Gram-negative bacteria. , 2010, The Journal of antimicrobial chemotherapy.

[5]  A. Raja,et al.  Drugs from the Natural Bio Sources for Human Disease , 2010 .

[6]  C. Sharma,et al.  Potency of Barleria prionitis L. bark extracts against oral diseases causing strains of bacteria and fungi of clinical origin , 2010 .

[7]  H. Kaur,et al.  Antibacterial Activity of Tea and Coffee: Their Extracts and Preparations , 2009 .

[8]  Kolapo Antimicrobial Activities of some Nigerian Chewing Sticks , 2009 .

[9]  M. Doble,et al.  Synergism between natural products and antibiotics against infectious diseases. , 2008, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[10]  L. Piddock,et al.  Bacterial efflux pump inhibitors from natural sources. , 2007, The Journal of antimicrobial chemotherapy.

[11]  N. A. Sukati,et al.  Some Swazi phytomedicines and their constituents , 2007 .

[12]  L. Piddock Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria , 2006, Clinical Microbiology Reviews.

[13]  H. Chambers,et al.  The changing epidemiology of Staphylococcus aureus? , 2001, Emerging infectious diseases.

[14]  K. Lewis,et al.  Flavonolignan and flavone inhibitors of a Staphylococcus aureus multidrug resistance pump: structure-activity relationships. , 2001, Journal of medicinal chemistry.

[15]  Angela Lee,et al.  Identification and Characterization of Inhibitors of Multidrug Resistance Efflux Pumps in Pseudomonas aeruginosa: Novel Agents for Combination Therapy , 2001, Antimicrobial Agents and Chemotherapy.

[16]  K. Lewis,et al.  Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Mary Jane Ferraro,et al.  Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically : approved standard , 2000 .

[18]  Michael E. Johnson,et al.  Multiple Novel Inhibitors of the NorA Multidrug Transporter of Staphylococcus aureus , 1999, Antimicrobial Agents and Chemotherapy.

[19]  G. Kaatz,et al.  Effects of NorA Inhibitors on In Vitro Antibacterial Activities and Postantibiotic Effects of Levofloxacin, Ciprofloxacin, and Norfloxacin in Genetically Related Strains ofStaphylococcus aureus , 1999, Antimicrobial Agents and Chemotherapy.

[20]  K. Lewis,et al.  Bacteria lacking a multidrug pump: a sensitive tool for drug discovery. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  V. Bidnenko,et al.  Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. , 1991, Proceedings of the National Academy of Sciences of the United States of America.