Bacterial cytological profiling reveals interactions between jumbo phage φKZ infection and cell wall active antibiotics in Pseudomonas aeruginosa

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 mi...

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Bibliographic Details
Published in:PloS one 2023-07, Vol.18 (7), p.e0280070-e0280070
Main Authors: Tsunemoto, Hannah, Sugie, Joseph, Enustun, Eray, Pogliano, Kit, Pogliano, Joe
Format: Article
Language:English
Subjects:
Antibiotic resistance
Antibiotics
Bacteria
Biology and Life Sciences
Ceftazidime
Cell walls
Enzymes
Fluorescence
Fluorescence microscopy
Infections
Medicine and Health Sciences
Microscopy
Molecular modelling
Morphology
Nuclei (cytology)
Phages
Physical Sciences
Proteins
Pseudomonas aeruginosa
Replication
RNA polymerase
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0280070