Bacterial resistance modifying tetrasaccharide agents from Ipomoea murucoides

Area of Science:

• Natural Product Chemistry
• Microbiology
• Pharmacology

Background:

• Bacterial multidrug resistance (MDR) is a significant global health threat.
• Efflux pumps are a major mechanism contributing to MDR in bacteria, particularly in Staphylococcus aureus.
• Natural products offer a promising source for novel MDR modulators.

Purpose of the Study:

• To isolate and characterize lipophilic tetrasaccharide inhibitors of bacterial multidrug efflux pumps from Ipomoea murucoides.
• To evaluate the antibacterial and resistance-modifying activities of these compounds against Staphylococcus aureus.

Main Methods:

• CHCl(3)-soluble extract of Ipomoea murucoides flowers was analyzed using preparative-scale recycling HPLC.
• Structures of isolated compounds were elucidated using spectroscopic methods.
• In vitro antibacterial and resistance-modifying activities were tested against Staphylococcus aureus strains, including those over-expressing MDR efflux pumps.

Main Results:

• Five lipophilic tetrasaccharides, murucoidins XII-XVI, were isolated.
• Murucidin XIV demonstrated direct antimicrobial activity against a norfloxacin-resistant Staphylococcus aureus strain (SA-1199B) with a MIC of 32 µg/ml.
• The other four compounds, while inactive alone, potentiated norfloxacin susceptibility by 4-fold at 25 µg/ml, with murucidin XIV showing similar potentiation at a lower concentration of 5 µg/ml.

Conclusions:

• Ipomoea murucoides flowers contain novel tetrasaccharide derivatives with potential to modulate bacterial multidrug resistance.
• Murucidin XIV exhibits both antimicrobial and resistance-modifying properties.
• These compounds, particularly murucidin XIV, warrant further investigation as potential agents against multidrug-resistant Staphylococcus aureus infections.