Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents

Area of Science:

• Antimicrobial research
• Mitochondrial targeted antioxidants
• Bacterial membrane interactions

Background:

• Mitochondria-targeted antioxidants (MTAs) are explored for therapeutic applications and substance delivery.
• MitoQ and SkQ1 are well-studied MTAs; SkQR1 is a fluorescent rhodamine analog of SkQ1.
• Understanding MTA interactions with bacterial efflux pumps and membranes is crucial.

Purpose of the Study:

• To investigate the antibacterial activity of SkQR1 and related rhodamine derivatives.
• To determine the susceptibility of Gram-positive and Gram-negative bacteria to SkQR1.
• To explore the role of multidrug resistance (MDR) pumps in the efficacy of these compounds.

Main Methods:

• Antibacterial assays against various bacterial strains, including wild-type and mutant Escherichia coli.
• Assessment of SkQR1 and rhodamine ester efflux by the AcrAB-TolC MDR pump.
• Fluorescence correlation spectroscopy and fluorescence microscopy to study SkQR1 localization.

Main Results:

• SkQR1 exhibited potent antibacterial activity against Gram-positive bacteria (e.g., Staphylococcus aureus, Mycobacterium smegmatis) but minimal effect on Gram-negative bacteria.
• The AcrAB-TolC pump did not efflux SkQR1 or C12R1, unlike SkQ1.
• Rhodamine derivatives C4R1 and C2R1 showed efficacy against ΔtolC E. coli but were less effective against wild-type E. coli.
• SkQR1 was observed to accumulate in the bacterial membrane.

Conclusions:

• SkQR1 possesses significant antibacterial properties, particularly against Gram-positive bacteria, with a distinct mechanism from SkQ1.
• Bacterial efflux pumps play a role in the differential activity of some rhodamine derivatives.
• SkQR1 accumulates in bacterial membranes, suggesting it as a potential agent for membrane-associated studies, but caution is advised when presenting it as a simple fluorescent analog of SkQ1 for visualization.