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Updated: Jul 5, 2025
Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes
Published on: March 2, 2020
Insights into colistin-mediated fluorescence labelling of bacterial LPS
Saurodeep Mandal1, Dipanwita Patra2, Sukhendu Mandal2
1Department of Chemistry, Siksha Bhavana, Visva-Bharati Santiniketan 731235 West Bengal India prithidipa.sahoo@visva-bharati.ac.in saurodeep@outlook.com gourabkanti.das@visva-bharati.ac.in.
Abstract:
Gram-negative bacterial infections are becoming untreatable due to their ability to mutate, and the gradual development of their resistance to the available antimicrobials. In recent times colistin, a drug of last resort, started losing its efficacy towards multidrug-resistant bacterial infections. Colistin targets bacterial endotoxin lipopolysaccharides (LPS) and destabilises the cytoplasmic membrane by disrupting the outer LPS membrane. In this study, we have tried to label the bacterial LPS, the main constituent of the cytoplasmic membrane of bacterial cells, to try to understand the interaction mechanism of LPS with colistin. The chemosensor, naphthaldehyde appended furfural (NAF) that selectively recognises colistin can label LPS, by showing its fluorescence signals. The computationally derived three-dimensional structure of LPS has been introduced to speculate on the possible binding mode of colistin with LPS, and this was also thoroughly studied with the help of quantum mechanics and molecular dynamics energy minimisation. Fluorescence microscopy and FE-SEM microscopic studies were also used to observe the change in the structural morphology of colistin-sensitive and resistant Salmonella typhi in different experimental conditions.
Insights
Researchers developed a novel fluorescent sensor to visualize how colistin interacts with lipopolysaccharides (LPS) in bacteria. This helps understand drug resistance mechanisms in multidrug-resistant infections.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- Gram-negative bacterial infections pose a growing threat due to antimicrobial resistance.
- Colistin, a last-resort antibiotic, is losing efficacy against multidrug-resistant strains.
- Colistin targets bacterial lipopolysaccharides (LPS) to destabilize the cell membrane.
Purpose of the Study:
- To understand the interaction mechanism between colistin and bacterial LPS.
- To develop a method for labeling LPS to study colistin binding.
- To investigate structural changes in bacteria upon colistin exposure.
Main Methods:
- Utilized a novel fluorescent chemosensor (naphthaldehyde appended furfural - NAF) to label LPS.
- Employed computational modeling (3D structure, quantum mechanics, molecular dynamics) to predict colistin-LPS binding.
- Applied fluorescence microscopy and FE-SEM to observe bacterial morphology changes.
Main Results:
- The NAF sensor successfully labeled bacterial LPS, showing fluorescence signals.
- Computational studies provided insights into the potential binding modes of colistin with LPS.
- Microscopic analyses revealed morphological alterations in colistin-sensitive and resistant *Salmonella typhi*.
Conclusions:
- The developed fluorescent sensor enables visualization of colistin-LPS interactions.
- Understanding these interactions is crucial for combating antimicrobial resistance.
- This approach aids in developing strategies against multidrug-resistant Gram-negative bacteria.
