The emergence of antibiotic-resistant bacteria has presented an increasing challenge to infection control. In general, bacterial populations commonly harbor phenotypic variants, known as persister cells, which are metabolically inactive and extremely tolerant to antibiotics. The persister cells are well known to survive conventional antibacterial treatments and regenerate the bacterial populations with a similar percentage of persister cellswhen the antibiotic treatment is stopped. The electrochemical control of persister cells (ECCP) presents a great potential for the treatment of chronic infections. We demonstrated that bacterial persister cells could be effectively eliminated by low-level direct currents (DCs) alone, and in synergy with antibiotics.  The discovery showedthat DC treatments could affect surface charge and membrane integrity of P. aeruginosa and increase intracellular interaction of metal cations and antibiotics with nucleic acid.

. Frontier in Science-1.001Moreover, electrochemical treatments mediated via carbon electrodes can also provoke the permeabilization of the cells to extracellular materials and lead to complete eradication of the persisters. These findings, corroborated by DNA microarray analysis, reveal that DC treatments have profound effects on the physiology of persister cells, altering the regulation of genes involved in antibiotic resistance, pyocin-related functions, and SOS response. The safety and efficacy of ECCP is further tested in co-culture models with human epithelial cells and P. aeruginosa PAO1 and in rabbit model of sinus infections. Overall, the study aims to improve the understanding of the electrophysiology of bacterial persister cells, and provided new insight for designing novel systems to effectively control infections associated with biofilms and persister cells.

The following images illustrate an electrochemical treatment of bacterial cells. The treatments disrupt the membrane functions of the cells and render them susceptible to antibiotics.

1. AMB expressSzkotak R, Niepa THR, Jawrani N, Gilbert JL, Jones MB, Ren D., Differential Gene Expression to Investigate the Effects of Low-level Electrochemical Currents on Bacillus Subtilis. AMB Express (2011).

2. BiomaterialsNiepa THR, Gilbert JL, & Ren D, Controlling Pseudomonas aeruginosa persister cells by weak electrochemical currents and synergistic effects with tobramycin. Biomaterials (2012), 33(30):7356-7365.

3. Niepa THR, Snepenger LM, Wang H, Sivan S, Gilbert JL, Jones MB, Ren D, Sensitizing Pseudomonas aeruginosa to antibiotics by electrochemical disruption of membrane functions, Biomaterials (2015), doi: 10.1016/j.biomaterials.2015.10.007.

Acta_Biomaterialia4. Niepa THR, Hao Wang, Dabrowiak JC, Gilbert JL, and Ren D. Synergy between tobramycin and trivalent chromium ion in electrochemical control of Pseudomonas aeruginosa. Acta Biomaterialia 36 (2016) 286–295.

Acta_Biomaterialia5. Niepa THR, Wang H, Gilbert JL, and Ren D., Eradication of Pseudomonas aeruginosa cells by cathodic electrochemical currents delivered with graphite electrodes.  Acta Biomaterialia (2016) Accepted.