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Published on: April 18, 2019
Synergistic Bactericidal Effects of R- and F-Type Pyocin Cocktails Against Clinical Pseudomonas aeruginosa Isolates
Yi-Luen Shen1,2, Wen-Tong Xu3,4, Zih-Ling Jiang4
1Division of Chest Medicine, Department of Internal Medicine, Asia University Hospital, Asia University, Taichung 413505, Taiwan.
Abstract:
Background/Objectives: Pseudomonas aeruginosa is a major cause of healthcare-associated infections, and the global rise of multidrug-resistant (MDR) strains has created an urgent need for alternative therapeutics. R- and F-type pyocins are phage tail-like bacteriocins that selectively kill P. aeruginosa by binding to lipopolysaccharide (LPS) receptors. We characterized O-serotype distribution and pyocin susceptibility among clinical isolates from central Taiwan to evaluate their therapeutic potential. Methods: A total of 109 ICU-derived P. aeruginosa isolates were analyzed. O-serotypes were determined by PCR, and pyocin gene carriage was confirmed by sequencing. Purified R1, R2, R5, F1, F2, F4, F7, and F12 pyocins were tested using spot assays. LPS profiles were examined by SDS-PAGE to explore structural correlates of resistance. Synergistic effects of combined R- and F-type pyocins were assessed in MDR isolates. Results: The most prevalent serotypes were O6 (23.9%), O2/O5/O16/O18/O20 (20.2%), O1 (16.5%), and O11/O17 (15.6%). Susceptibility was strongly serotype-dependent: O1 and O6 were highly sensitive to both pyocin types, whereas the O2/O5/O16/O18/O20 group showed marked resistance. SDS-PAGE demonstrated that resistant isolates possessed densely packed long-chain O-antigens, likely shielding LPS core receptors from pyocin binding. F-type pyocins exhibited bactericidal activity comparable to R-types, and R/F pyocin cocktails produced synergistic killing against MDR isolates. Conclusions: These findings provide an updated serotype profile of P. aeruginosa in Taiwan and highlight the importance of LPS structural variability in pyocin susceptibility. These results underscore the potential of pyocin-based cocktails as a promising precision-medicine strategy to inhibit the planktonic growth and biofilm formation of multidrug-resistant P. aeruginosa isolates.
Insights
Pyocins show promise against multidrug-resistant Pseudomonas aeruginosa. Serotype variations in lipopolysaccharide (LPS) affect susceptibility, suggesting pyocin cocktails could be a precision medicine approach.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriophage Therapy
Background:
- Pseudomonas aeruginosa is a significant cause of healthcare-associated infections.
- Multidrug-resistant (MDR) strains necessitate novel therapeutic strategies.
- R- and F-type pyocins are bacteriocins targeting P. aeruginosa.
Purpose of the Study:
- To determine O-serotype distribution and pyocin susceptibility in P. aeruginosa clinical isolates from Taiwan.
- To evaluate the therapeutic potential of pyocins against MDR P. aeruginosa.
- To investigate the correlation between LPS structure and pyocin resistance.
Main Methods:
- Analysis of 109 ICU-derived P. aeruginosa isolates.
- O-serotyping by PCR and pyocin gene confirmation by sequencing.
- Testing pyocin susceptibility using spot assays and SDS-PAGE for LPS profiling.
Main Results:
- Prevalent serotypes included O6, O2/O5/O16/O18/O20, O1, and O11/O17.
- Pyocin susceptibility varied significantly by serotype, with O1 and O6 being sensitive and O2/O5/O16/O18/O20 resistant.
- Resistant isolates had densely packed O-antigens, hindering pyocin binding.
- R- and F-type pyocin cocktails demonstrated synergistic killing of MDR isolates.
Conclusions:
- Updated P. aeruginosa serotype profile for Taiwan established.
- LPS structural variations are critical determinants of pyocin susceptibility.
- Pyocin cocktails represent a potential precision medicine strategy against MDR P. aeruginosa growth and biofilm formation.
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