Real-time size transformation of membrane pores (permeability) and efflux kinetics in three mutants of P. aeruginosa, WT, nalB-1, and AABM, have been directly observed in the presence of 0, 25, and 250 ^g/mL chloramphenicol using nanoparticle optics and single-live-cell imaging. The membrane permeability in P. aeruginosa (WT, nalB-1, AABM) increased as the chloramphenicol concentration increased from 0 to 250 ^g/mL and as the incubation time increased (Fig. 4), indicating the real-time size transformation of membrane pores (permeability). The results suggest that the mechanism of multi-antibiotic resistance may include the induction of transformation of membrane permeability and intrinsic efflux pump machinery. This work constitutes the first direct observation of the size transformation of membrane pores (permeability) and the interplay of membrane permeability and efflux kinetics in real time at single-live-cell resolution and offers the new possibility of advancing the understanding of multidrug resistance. This study demonstrates the possibility of using nanoparticles for the study of the real-time transformation of membrane permeability in eukaryotic cells (tumor) for better understanding of multidrug resistance. We are currently developing nano-particle optics for the study of the real-time transformation of electropermeabilization [75, 76] for a better understanding of the effect of radio frequency (RF) and electric fields on membrane permeability.
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