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Updated: Dec 2, 2025
Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
Membrane-Targeting Triphenylphosphonium Functionalized Ciprofloxacin for Methicillin-Resistant Staphylococcus aureus
Sangrim Kang1, Kyoung Sunwoo2, Yuna Jung3
1Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Korea.
Abstract:
Multidrug-resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach, modification of an antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-amide-PPh3) to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3, and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (methicillin-resistant S. aureus (MRSA)) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivatives induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.
Insights
Researchers modified ciprofloxacin (CFX) with triphenylphosphonium (TPP) to create new antibiotics targeting multidrug-resistant (MDR) bacteria. These TPP-conjugated CFX derivatives show enhanced activity against MRSA, inhibiting growth and biofilm formation.
Area of Science:
- Medicinal Chemistry
- Microbiology
- Drug Discovery
Background:
- Multidrug-resistant (MDR) bacteria pose a significant global public health threat.
- Developing novel antibiotics against MDR strains is a challenging and lengthy process.
- Targeting bacterial membranes offers a potential strategy to overcome existing resistance mechanisms.
Purpose of the Study:
- To synthesize and evaluate novel ciprofloxacin (CFX) derivatives conjugated with triphenylphosphonium (TPP) moiety.
- To assess the antibacterial activity of these derivatives against a panel of bacteria, including MDR strains.
- To investigate the impact of TPP conjugation on bacterial membrane integrity, biofilm formation, and resistance gene expression.
Main Methods:
- Synthesis of CFX-ester-PPh3 and CFX-amide-PPh3 via ester and amide coupling.
- Minimum Inhibitory Concentration (MIC) assays against 16 bacterial species, including MDR strains.
- Morphological monitoring using microscopy and analysis of resistance-related gene expression.
Main Results:
- TPP-conjugated CFX derivatives demonstrated significantly enhanced antibacterial activity against Gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA).
- CFX-amide-PPh3 exhibited potent activity against MRSA ST5 5016, with MIC values as low as 2.78 µg/mL.
- CFX derivatives effectively inhibited MRSA biofilm formation (up to 74.9% inhibition by CFX-amide-PPh3) and induced significant morphological changes and reduced resistance gene expression.
Conclusions:
- Triphenylphosphonium (TPP) conjugation is a viable strategy to enhance the antibacterial efficacy of existing antibiotics like ciprofloxacin.
- The developed TPP-conjugated CFX derivatives show promise as novel agents to combat challenging MDR bacterial infections, including MRSA.
- This modification approach offers a potentially straightforward method for developing new antimicrobial therapies that can be prepared at clinical sites.
