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Bacterial cytological profiling reveals interactions between jumbo phage φKZ infection and cell wall active
Hannah Tsunemoto1, Joseph Sugie1, Eray Enustun1
1Division of Biological Sciences, University of California, San Diego, San Diego, CA, United States of America.
Abstract:
The emergence of antibiotic resistance in bacteria has led to the investigation of alternative treatments, such as phage therapy. In this study, we examined the interactions between the nucleus-forming jumbo phage ФKZ and antibiotic treatment against Pseudomonas aeruginosa. Using the fluorescence microscopy technique of bacterial cytological profiling, we identified mechanism-of-action-specific interactions between antibiotics that target different biosynthetic pathways and ФKZ infection. We found that certain classes of antibiotics strongly inhibited phage replication, while others had no effect or only mildly affected progression through the lytic cycle. Antibiotics that caused an increase in host cell length, such as the cell wall active antibiotic ceftazidime, prevented proper centering of the ФKZ nucleus via the PhuZ spindle at midcell, leading us to hypothesize that the kinetic parameters of the PhuZ spindle evolved to match the average length of the host cell. To test this, we developed a computational model explaining how the dynamic properties of the PhuZ spindle contribute to phage nucleus centering and why some antibiotics affect nucleus positioning while others do not. These findings provide an understanding of the molecular mechanisms underlying the interactions between antibiotics and jumbo phage replication.
Insights
Investigating phage therapy for antibiotic-resistant Pseudomonas aeruginosa, this study reveals how antibiotics impact jumbo phage ФKZ replication. Certain antibiotics inhibit phage growth, while others disrupt phage nucleus positioning by altering host cell shape.
Area of Science:
- Microbiology
- Molecular Biology
- Biophysics
Background:
- Antibiotic resistance necessitates novel therapeutic strategies like phage therapy.
- Jumbo phages, such as ФKZ, offer potential in combating bacterial infections.
- Understanding phage-antibiotic interactions is crucial for effective treatment development.
Purpose of the Study:
- To investigate the interplay between jumbo phage ФKZ and antibiotic treatments against Pseudomonas aeruginosa.
- To elucidate the mechanism-of-action-specific interactions between different antibiotic classes and phage infection.
- To explore how antibiotics affect phage nucleus formation and positioning.
Main Methods:
- Bacterial cytological profiling using fluorescence microscopy.
- Assessing phage replication and lytic cycle progression under various antibiotic treatments.
- Computational modeling of phage nucleus dynamics and positioning.
Main Results:
- Specific antibiotics significantly inhibited ФKZ phage replication.
- Cell wall-active antibiotics, like ceftazidime, disrupted ФKZ nucleus centering by affecting the PhuZ spindle.
- A computational model explained the role of PhuZ spindle dynamics in nucleus positioning and antibiotic influence.
Conclusions:
- Antibiotic choice critically influences jumbo phage replication and infection dynamics.
- Phage nucleus positioning is sensitive to host cell morphology changes induced by certain antibiotics.
- This research provides insights into the molecular mechanisms governing phage-antibiotic interactions.
