Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus.

Khellin and visnagin are natural furanochromones that photoreact with DNA. Khellin has been used in the treatment of vitiligo and psoriasis, as well as in the treatment of angina pectoris and asthma due to its potent action as a coronary vasodilator and antispasmodic agent. The present study aimed to investigate whether the compounds khellin and visnagin act as inhibitors of NorA protein, an efflux pump overproduced by the strain of Staphylococcus aureus SA-1199B that confers resistance to the fluoroquinolones, such as norfloxacin and ciprofloxacin. These substances alone did not show antibacterial activity against the strain tested. On the other hand, when these compounds were added to the culture medium at subinhibitory concentration, they were able to reduce the minimum inhibitory concentration (MIC) of norfloxacin, ethidium bromide, as well as berberine, suggesting that these compounds are modulating agents of norfloxacin resistance, possibly due to NorA inhibition. Molecular docking analysis showed that both khellin and visnagin form hydrogen bonds with Arg310, an important residue in the interaction between NorA and its substrates, supporting the hypothesis that these compounds are NorA inhibitors. These results suggest a possible application of khellin and visnagin as adjuvants to norfloxacin in the treatment of infections caused by strains of S. aureus that overproduce NorA.

Modulation of the Drug Resistance by Platonia insignis Mart. Extract, Ethyl Acetate Fraction and Morelloflavone/Volkensiflavone (Biflavonoids) in Staphylococcus aureus Strains Overexpressing Efflux Pump Genes.

BACKGROUND: Microbial resistance to antibiotics is a global public health problem, which requires urgent attention. Platonia insignis is a native species from the eastern Brazilian Amazon, used in the treatment of burns and wounds. OBJECTIVES: To evaluate the antimicrobial activity of the hydroalcoholic extract of P. insignis (PIHA), the ethyl acetate fraction (PIAE), and its subfraction containing a mixture of biflavonoids (BF). Moreover, the effect of these natural products on the antibiotic activity against S. aureus strains overexpressing efflux pump genes was also evaluated. METHODS: Minimal inhibitory concentrations were determined against different species of microorganisms. To evaluate the modulatory effect on the Norfloxacin-resistance, the MIC of this antibiotic was determined in the absence and presence of the natural products at subinhibitory concentrations. Inhibition of the EtBr efflux assays were conducted in the absence or presence of natural products. RESULTS: PIHA showed a microbicidal effect against S. aureus and C. albicans, while PIAE was bacteriostatic for S. aureus. PIAE and BF at subinhibitory concentrations were able to reduce the MIC of Norfloxacin acting as modulating agents. BF was able to inhibit the efflux of EtBr efflux in S. aureus strains overexpressing specific efflux pump genes. CONCLUSION: P. inignisis, a source of efflux pump inhibitors, including volkensiflavone and morelloflavone, which were able to potentiate the Norfloxacin activity by NorA inhibition, being also able to inhibit QacA/B, TetK and MsrA. Volkensiflavone and morelloflavone could be used as an adjuvant in the antibiotic therapy of multidrug resistant S. aureus strains overexpressing efflux pumps.

Enhancement of the antibiotic activity of aminoglycosides by extracts from Anadenanthera colubrine (Vell.) Brenan var. cebil against multi-drug resistant bacteria.

The aim of this work was to evaluate the antimicrobial activity of ethanol (EEAC) and hexane (HFAC) extracts from the stem bark of Anadenanthera colubrina (Vell.) Brenan var. cebil alone or in combination with aminoglycosides against multi-drug resistant (MDR) bacteria. Minimal inhibitory concentrations (MICs) of the extracts were determined by using microdilution assay. For the evaluation of extracts as modulators of antibiotic resistance, MICs of neomycin and amikacin were determined in presence or absence of each compound at sub-inhibitory concentrations. Both EEAC and HFAC did not show antimicrobial activity against MDR strains tested. However, the addition of EEAC and HFAC enhanced the activity of neomycin and amikacin against Staphylococcus aureus SA10 strain. When the natural products were replaced by chlorpromazine, the same effect was observed. Anadenanthera colubrine var. cebil may be a source of phytochemicals able to potentiate the aminoglycoside activity against MDR S. aureus by the inhibition of efflux pump.

Light-mediated antibacterial activity of Lippia origanoides H.B.K. in vitro.

An ethanol extract and different partition fractions obtained from Lippia origanoides H.B.K. were assayed for light-mediated activity against strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Identical assays were conducted with and without exposure to UV-A (400-315 nm) light to test for light enhanced activity. The ethanol extract and dichloromethane fraction showed light-mediated activity against the S. aureus strain, but not against the E. coli strain. The dichloromethane fraction was more active than the ethanol extract. Naringenin did not display light-mediated activity against the tested bacteria, indicating that the light-mediated antimicrobial activity of the dichloromethane fraction is not due to its major component. The results represent the first report of light-mediated antimicrobial activity of Lippia origanoides and show that its phytochemicals could be used as light-mediated antimicrobial agents.