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Phage-based decontamination: Exploring resistance, disinfectant tolerance, and virulence trade-offs in Acinetobacter
Yi-Ting Chen1, Li-Kuang Chen2, Ruei-Sen Jiang3
1Department and Graduate Institute of Public Health, Tzu Chi University, Hualien, Taiwan.
Abstract:
Increasing multidrug resistance in Acinetobacter baumannii necessitates a better understanding of how phage resistance influences bacterial fitness, disinfectant tolerance, and virulence. In this study, we induced phage-resistant mutants from the reference strain ATCC 17978 using phages previously applied in clinical decontamination, and we evaluated their physiological adaptations. The wild-type strain initially showed high phage susceptibility but rapidly developed resistance within 24 h. Phage-resistant mutants exhibited changes in plaque morphology and developed at frequencies between 7.6 × 10⁻⁷ and 2.11 × 10⁻⁵. In many cases, these mutants required alternative phages for successful reinfection. Certain phage-resistant strains (e.g., 2R and RB71RR) showed initial fitness reductions (15-20 % fewer generations), which were restored to wild-type levels after 24 h. Whole-genome sequencing of JB68R revealed mutations in glycosyltransferases, IS3 transposases, and peptidoglycan DD-metalloendopeptidases, which correlated with increased ethanol sensitivity (50 %) and enhanced NaDCC tolerance-suggesting potential membrane remodeling as an adaptive mechanism. All phage-resistant mutants exhibited reduced virulence in a Galleria mellonella model, as indicated by lower mortality and melanization responses. To provide a comparative perspective, we also examined colistin-resistant strains generated from ATCC 17978, given the critical role of colistin as a last-line antibiotic. These strains displayed persistent growth impairment (22 % reduced generation number, 32 % lower growth rate; p < 0.01) alongside increased tolerance to hydrogen peroxide (3.3-fold) and benzalkonium chloride (2-fold), indicating a distinct set of resistance trade-offs. These findings underscore the ecological and physiological differences between phage and antibiotic resistance and highlight exploitable vulnerabilities, which could guide the development of more effective, integrated infection control strategies in healthcare settings.
Insights
Phage resistance in Acinetobacter baumannii alters bacterial fitness and disinfectant tolerance, offering insights into new infection control strategies. These findings reveal distinct trade-offs compared to antibiotic resistance.
Area of Science:
- Microbiology
- Bacterial Genetics
- Antimicrobial Resistance
Background:
- Multidrug resistance in Acinetobacter baumannii poses a significant clinical challenge.
- Understanding phage resistance mechanisms is crucial for developing novel therapeutic and decontamination strategies.
Purpose of the Study:
- To investigate the physiological adaptations of Acinetobacter baumannii upon developing resistance to bacteriophages.
- To compare the trade-offs associated with phage resistance versus colistin resistance.
Main Methods:
- Induction of phage-resistant mutants from Acinetobacter baumannii ATCC 17978.
- Evaluation of bacterial fitness, disinfectant tolerance, and virulence in a Galleria mellonella model.
- Whole-genome sequencing of selected phage-resistant mutants.
- Comparative analysis with colistin-resistant strains.
Main Results:
- Phage-resistant mutants showed altered plaque morphology and varying resistance frequencies.
- Some mutants exhibited initial fitness reductions that were later restored.
- Genomic analysis revealed mutations linked to increased ethanol sensitivity and NaDCC tolerance.
- All phage-resistant mutants displayed reduced virulence in the Galleria mellonella model.
- Colistin-resistant strains showed persistent growth impairment and increased tolerance to hydrogen peroxide and benzalkonium chloride.
Conclusions:
- Phage resistance in Acinetobacter baumannii involves distinct physiological trade-offs compared to antibiotic resistance.
- These adaptations present potential vulnerabilities that can be exploited for infection control.
- Findings support the development of integrated strategies combining phage therapy and other antimicrobials.
