Cellular heterogeneity in the response of Burkholderia thailandensis to antibiotics and phages in synthetic spatial refuges

The study of the complex interactions between phage, antibiotics, and bacteria is crucial for the development of rational phage-antibiotic therapies. Traditionally, these interactions have been studied using bulk assays, which often obscure cellular heterogeneities and the impact of spatial refuges on phage and antibiotic efficacy.

To address this, researchers employed microfluidics-based time-lapse microscopy to investigate the response of Burkholderia thailandensis to phage {Phi}Bp-AMP1 and sub-inhibitory concentrations of two antibiotics, ciprofloxacin and trimethoprim.

The researchers discovered significant phenotypic heterogeneity in the response of B. thailandensis to the antibiotics and phage. When exposed to both ciprofloxacin and phage simultaneously, the size of individual B. thailandensis cells decreased. On the other hand, exposure to phage and trimethoprim together resulted in a slower cell doubling rate.

The presence of ciprofloxacin led to prolonged phage lysis of B. thailandensis, which was preceded by a noticeable pause in cell elongation. In contrast, trimethoprim constrained phage lysis.

These findings reveal that the interactions between antibiotics and phage have distinct effects on bacterial subpopulations within spatial refuges, which are notoriously challenging to treat with antibiotics. The study highlights the importance of understanding these complex interactions to develop effective phage-antibiotic therapies.