Persisters: a distinct physiological state of E. coli

By Devang T. Shah, Zhigang Zhang, Arkady B. Khodursky, N. Kaldalu, Kristiina Kurg, Kim Lewis. BMC Microbiology, 2006

638 citations recorded by the source corpus.

BackgroundBacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understanding persisters is encouraging, but the main obstacle in understanding their nature was our inability to isolate these elusive cells from a wild-type population since their discovery in 1944.ResultsWe hypothesized that persisters are dormant cells with a low level of translation, and used this to physically sort dim E. coli cells which do not contain sufficient amounts of unstable GFP expressed from a promoter whose activity depends on the growth rate. The dim cells were tolerant to antibiotics and exhibited a gene expression profile distinctly different from those observed for cells in exponential or stationary phases. Genes coding for toxin-antitoxin module proteins were expressed in persisters and are likely contributors to this condition.ConclusionWe report a method for persister isolation and conclude that these cells represent a distinct state of bacterial physiology.

Subfields: Endocrinology, Genetics

View Paper: https://www.semanticscholar.org/paper/71288170026ef8f9eb15d371f2601133ecbd240c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology

1. Kim Lewis
2. P. Stoodley
3. L. Hall-Stoodley
4. C. Beloin
5. D. Lebeaux
6. J. Ghigo
7. J. Kaplan
8. R. Aminov

In Genetics

1. J. Ghigo
2. C. Beloin
3. D. Lebeaux
4. Thomas K. Wood
5. Brian W. Kwan
6. S. Knabel
7. Tobias Dörr
8. M. Vulić

Citations in the corpus

• Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance (2020, background): “Thus, by inactivating antibiotic targets, TA confers antibiotic tolerance [101] and increases persister formation [102] (Figure 3C).”
• Ciprofloxacin Causes Persister Formation by Inducing the TisB toxin in Escherichia coli (2010, background): “Isolated persisters show increased expression levels of chromosomal toxin/antitoxin (TA) genes [9,12].”
• Multidrug tolerance of biofilms and persister cells. (2008, background): “Based on these data, we reasoned that dormancy may be used to physically sort naive persister cells from a wild type population ( Shah et al. 2006 ).”
• Evolving concepts in biofilm infections (2009, background): “contribute to a generalized resistance or tolerance to antibiotics (Brown et al., 1988; Anwar et al., 1992; Stewart and Costerton, 2001; Borriello et al., 2004; 2006; Shah et al., 2006).”
• Cryptic prophages help bacteria cope with adverse environments (2010, background): “In addition, 24 cryptic prophage genes have been linked to persistence, including the relE toxin gene of Qin and the yeeV toxin gene of CP4-4”
• Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics (2014, background): “coli cells with low ribosomal activity that had been demonstrated to be enriched in persisters (93).”
• Persister cells, dormancy and infectious disease (2007, background): “Based on these data, we reasoned that dormancy could be used to physically sort naive persister cells (those that have not been exposed to antibiotics) from the populatio”
• Bacterial Persister Cell Formation and Dormancy (2013, methodology): “In addition to the original work of Bigger (4) and that related to TA systems (20), Kwan et al.”
• Multimetal resistance and tolerance in microbial biofilms (2007, background): “Studies using this bacterium suggest that persister cells are metabolically quiescent and express several genes that are associated with stress tolerance, such as chaperones, the multiple antibiotic resistance ( marRAB ) regulon and cold-shock protein”