(253g) Inactivation of Persister Cells by Low-Level Direct Currents
AIChE Annual Meeting
2009
2009 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Disease Therapies
Tuesday, November 10, 2009 - 2:40pm to 3:00pm
Recent
research has shown that a small percentage of cells in bacterial cultures are
non-growing persister cells. Although the mechanism of persister formation
remains elusive, it is well accepted that the persister cells are not mutants
with growth defects, but rather phenotypic variants of the wild-type strain.
The dormant nature of persister cells allows them to escape the killing by
antibiotics, presenting a great challenge to curing chronic infections. In this
presentation, we report for the first time that the persister cells can be
effectively inactivated by low-level direct currents (DCs). After treatment
with 75 µA/cm2 DC using graphite electrodes for 60 minutes, the
viable persister cells of Escherichia coli HM22 in 0.85% NaCl buffer
decreased from 5.7×105 to 9.4×102 CFU/mL. In contrast,
incubation for 60 minutes in 0.85% NaCl pretreated with the same level and
duration of DC only reduced the viable cells from 1.2×106 to 1.2×105
CFU/mL. In addition to inactivation by applying DC alone, synergistic
effects were observed when treating persister cells with DC and antibiotic
together. As expected, treatment with 100 µg/mL ampicillin
(Amp), 20 µg/mL cinoxacin (Cn) or 20 µg/mL tobramycin (Tb) alone only
caused slight reduction in the number of viable persister cells. In the
presence of 75 µA/cm2 DC, however, the viable persister cells were
reduced from 5.2×105 to 1.7×104 CFU/mL by 100 µg/mL Amp,
from 1.1×106 to 2.3CFU/mL by 20 µg/mL Cn, and from
1.0×106 to 23 CFU/mL by 20 µg/mL Tb. These data indicate that the
efficacy of Amp, Cn and Tb increased approximately by 30, 70000 and 12000 times
respectively by 75 µA/cm2 DC, compared to the treatments without DC.
The possible mechanism of these effects will be discussed. These results are
helpful for understanding the mechanism of persister formation and for
developing novel control methods.