Hypoionic shock treatment enables aminoglycosides antibiotics to eradicate bacterial persisters.

Liu Jiafeng,Xinmiao Fu,Zengyi Chang

doi:10.1038/srep14247

Abstract

Bacterial persisters, usually being considered as dormant cells that are tolerant to antibiotics, are an important source for recurrent infection and emergence of antibiotic resistant pathogens. Clinical eradication of pathogenic persisters is highly desired but greatly difficult mainly due to the substantial reduction in antibiotics uptake as well as the non-active state of the drug targets. Here we report that bacterial persisters (normal growing cells as well) can be effectively eradicated by aminoglycoside antibiotics upon hypoionic shock (e.g. pure water treatment) even for less than one minute. Such hypoionic shock potentiation effect on aminoglycosides is proton motive force-independent, and is apparently achieved by promoting the entrance of aminoglycosides, speculatively through the mechanosensitive ion channels. Our revelations may provide a simple and powerful strategy to eradicate pathogen persisters.

Highlights

A two-minute hypoionic shock treatment was found to enable tobramycin to efficiently eradicate conditioned E. coli persister cells (Fig. 2b), which were made insusceptible to antibiotics by treating exponential phase cells with bacteriostatic compound rifampicin (being an transcription inhibitor) or placing the cells at a low temperature of 4 °C (both for one hour)[7]
Such hypoionic shock are apparently effective for aminoglycoside antibiotics in general, as observed for streptomycin and kanamycin, but not for the other two major types of bactericidal antibiotics, either β -lactams that inhibit cell wall synthesis, or quinolones that inhibit DNA synthesis (Supplementary Fig. 3)
These observations implicate that hypoionic shock treatment promote the aminoglycoside type of antibiotics to eradicate E. coli persisters

Summary

Introduction

A two-minute hypoionic shock treatment was found to enable tobramycin to efficiently eradicate conditioned E. coli persister cells (Fig. 2b), which were made insusceptible to antibiotics by treating exponential phase cells with bacteriostatic compound rifampicin (being an transcription inhibitor) or placing the cells at a low temperature of 4 °C (both for one hour)[7]. We demonstrated that the potentiation effect of short-time hypoionic shock treatment for aminoglycoside antibiotic to eradicate E. coli persisters was found to be independent of the proton-motive force across the plasma membrane (Supplementary Fig. 6), as the persister-killing effect largely remained even in the presence of carbonyl cyanide m-chlorophenyl hydrazone (CCCP), an uncoupler that was previously reported to eliminate the proton-motive force and to abolish the uptake of aminoglycosides[11,15].

Results

Conclusion