GlpD and PlsB Participate in Persister Cell Formation in Escherichia coli
TLDR
Genetic studies of mutants affected in pathways involved in sn-glycerol-3-phosphate metabolism have led to the identification of two additional multidrug tolerance loci, glpABC, the anaerobic sn- Glycerol 3-Phosphate dehydrogenase, and plsB, an sn- glycerol -3- phosphate acyltransferase.Abstract:
Bacterial populations produce dormant persister cells that are resistant to killing by all antibiotics currently in use, a phenomenon known as multidrug tolerance (MDT). Persisters are phenotypic variants of the wild type and are largely responsible for MDT of biofilms and stationary populations. We recently showed that a hipBA toxin/antitoxin locus is part of the MDT mechanism in Escherichia coli. In an effort to find additional MDT genes, an E. coli expression library was selected for increased survival to ampicillin. A clone with increased persister production was isolated and was found to overexpress the gene for the conserved aerobic sn-glycerol-3-phosphate dehydrogenase GlpD. The GlpD overexpression strain showed increased tolerance to ampicillin and ofloxacin, while a strain with glpD deleted had a decreased level of persisters in the stationary state. This suggests that GlpD is a component of the MDT mechanism. Further genetic studies of mutants affected in pathways involved in sn-glycerol-3-phosphate metabolism have led to the identification of two additional multidrug tolerance loci, glpABC, the anaerobic sn-glycerol-3-phosphate dehydrogenase, and plsB, an sn-glycerol-3-phosphate acyltransferase.read more
Citations
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Physiological heterogeneity in biofilms.
TL;DR: The processes that generate chemical gradients inBiofilms, the genetic and physiological responses of the bacteria as they adapt to these gradients and the techniques that can be used to visualize and measure the microscale physiological heterogeneities of bacteria in biofilms are discussed.
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Persister cells, dormancy and infectious disease
TL;DR: The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.
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Distinguishing between resistance, tolerance and persistence to antibiotic treatment.
TL;DR: This Opinion article describes recent studies of tolerance, resistance and persistence, outlining how a clear and distinct definition for each phenotype can be developed from these findings and proposes a framework for classifying the drug response of bacterial strains according to these definitions that is based on the measurement of the minimum inhibitory concentration.
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Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics
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Book ChapterDOI
Multidrug tolerance of biofilms and persister cells.
TL;DR: Identification of persister genes opens the way to a rational design of anti-biofilm therapy and combination of a conventional antibiotic with a compound inhibiting persister formation or maintenance may produce an effective therapeutic.
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