Our results imply that there are no E. coli strains that have generally high or low levels of persisters; instead, there are different types of persister cells within populations, and each type may be more or less persistent to different antibiotics. Importantly, the variation in persister fractions exists even for antibiotics with nearly identical modes of LDN-193189 action (ciprofloxacin and nalidixic acid). Mechanistically, this suggests that persistence through cell dormancy is not a single, general phenomenon. Instead, check details there

may be distinct physiological states of dormancy, each of which is differently susceptible to a particular antibiotic. The idea that there are different types of persister cells that arise from a variety of mechanisms has also been proposed in a recently published study [34]. We note that one complicating factor in this interpretation is that these different persister populations may have different Eltanexor order propensities to form colonies, and that this might explain some of the differences in the shapes of the kill curves that we observed. However, given the range of persister fractions that we observed (over four orders of magnitude), we do not think that this mechanism can fully explain the patterns that we find. It is also possible that

although the isolates that we studied have similar MIC values, they differ in their pharmacodynamics [35]. However, the persister fraction should largely be independent of

the pharmacodynamic behavior; thus this is unlikely to account for the differences that we observe between isolates [34]. Evidence of two different types of persister cells has been shown previously by Balaban et al. [6], and genotypic changes at different loci were associated with each phenotype. Similarly, genetic differences between different E. coli isolates, such as the presence or absence of TA various modules, may affect the production of persister cells (Figure 6). Gefen et al. [36] suggested that large differences in the measurement of persister fractions might arise because antibiotic Ponatinib in vitro exposure begins at different stages of exponential growth (before or after 1.5 hours of growth). However, by growing the cells for four hours, we hope to have minimized such effects, and propose that the large differences we find in persister fractions are not due to differences in growth stage, but to fundamental differences in the mechanisms of persister production. We note that the set of environment isolates that we have used are not known to be pathogenic, suggesting that many of them have had less exposure to antibiotics and the concomitant selection for resistant or persister phenotypes that arises from such exposure.