Polyacylated neohesperidosides From Geranium caespitosum: bacterial multidrug resistance pump inhibitors

Stermitz, Frank R.; Cashman, Kevin K; Halligan, Kathleen M.; Morel, C; Tegos, George P.; Lewis, Kim

doi:10.1016/s0960-894x(03)00316-0

Cited by 59 publications

(25 citation statements)

References 15 publications

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“…It was suggested that plants could provide a rich source of MDR efflux pump inhibitors (EPIs) that could restore the activity of MDR efflux pump substrates even to synthetic agents such as fluoroquinolones (95). The search for natural agents that inhibit efflux by S. aureus has continued, and several compounds have been identified as potent inhibitors (131,152,209,210,212). Tegos and Lewis (216) determined the activity of several antimicrobials from plants, tetracycline and erythromycin, in the presence of two EPIs, MC207-110 (see below) and INF271 (118), for several species of bacteria, including P. aeruginosa, E. coli, S. enterica serovar Typhimurium, and S. aureus.…”

Section: Inhibitors Of Mdr Efflux Pumpsmentioning

confidence: 99%

Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

2006

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SUMMARY Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed.

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Section: Inhibitors Of Mdr Efflux Pumpsmentioning

confidence: 99%

Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

2006

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“…Several compounds, such as reserpine, behave as if they inhibit efflux pumps and hence have become known as efflux pump inhibitors (EPIs) [4]. Since that time, numerous phytochemicals have been shown to have activity against S. aureus or other Grampositive bacteria, or to act as potential EPIs with antimicrobials for Gram-positive bacteria [5][6][7][8][9][10][11]. Unfortunately, most of the plant-derived compounds have little or no activity with antibiotics against Gram-negative bacteria and it was suggested that, as many plant pathogens are Gram-negative bacteria, plants may not produce molecules effective against these organisms [5].…”

Section: Introductionmentioning

confidence: 99%

Medicinal plant extracts with efflux inhibitory activity against Gram-negative bacteria

Garvey

Rahman

Gibbons

et al. 2011

International Journal of Antimicrobial Agents

111

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“…The more highly acylated compound ADH7 had no direct activity against S. aureus but potentiated activity of the antibiotics berberine, rhein, ciprofloxacin, and norfloxacin (28).…”

Section: Discussionmentioning

confidence: 95%

“…Reserpine and phenylalanine-arginine-␤-naphthylamide (PA␤N) were obtained from Sigma-Aldrich (St. Louis, MO), INF271 was from Chembridge (San Diego, CA), and both 5-methoxyhydnocarpine and polyacetylated neohesperidoside (ADH7) (Fig. 1) were isolated from primary botanical material, as previously described (28,29). Stock solutions were prepared in dimethylsulfoxide or ethanol (PA␤N) at a concentration of 10 mM and stored at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

Inhibitors of Bacterial Multidrug Efflux Pumps Potentiate Antimicrobial Photoinactivation

Tegos

Masago

Fatima

et al. 2008

Antimicrob Agents Chemother

123

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Antimicrobial photodynamic inactivation (APDI) combines a nontoxic photoactivatable dye or photosensitizer (PS) with harmless visible light to generate singlet oxygen and reactive oxygen species that kill microbial cells. Cationic phenothiazinium dyes, such as toluidine blue O (TBO), are the only PS used clinically for APDI, and we recently reported that this class of PS are substrates of multidrug efflux pumps in both gram-positive and gram-negative bacteria. We now report that APDI can be significantly potentiated by combining the PS with an efflux pump inhibitor (EPI). Killing of Staphylococcus aureus mediated by TBO and red light is greatly increased by coincubation with known inhibitors of the major facilitator pump (NorA): the diphenyl urea INF271, reserpine, 5-methoxyhydnocarpin, and the polyacylated neohesperidoside, ADH7. The potentiation effect is greatest in the case of S. aureus mutants that overexpress NorA and least in NorA null cells. Addition of the EPI before TBO has a bigger effect than addition of the EPI after TBO. Cellular uptake of TBO is increased by EPI. EPI increased photodynamic inactivation killing mediated by other phenothiazinium dyes, such as methylene blue and dimethylmethylene blue, but not that mediated by nonphenothiazinium PS, such as Rose Bengal and benzoporphyrin derivative. Killing of Pseudomonas aeruginosa mediated by TBO and light was also potentiated by the resistance nodulation division pump (MexAB-OprM) inhibitor phenylalanine-arginine beta-naphthylamide but to a lesser extent than for S. aureus. These data suggest that EPI could be used in combination with phenothiazinium salts and light to enhance their antimicrobial effect against localized infections.

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Polyacylated neohesperidosides From Geranium caespitosum: bacterial multidrug resistance pump inhibitors

Cited by 59 publications

References 15 publications

Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria

Medicinal plant extracts with efflux inhibitory activity against Gram-negative bacteria

Inhibitors of Bacterial Multidrug Efflux Pumps Potentiate Antimicrobial Photoinactivation

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