scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Bacterial Persistence as a Phenotypic Switch

10 Sep 2004-Science (American Association for the Advancement of Science)-Vol. 305, Iss: 5690, pp 1622-1625
TL;DR: Investigating the persistence of single cells of Escherichia coli with the use of microfluidic devices found phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates, leading to a simple mathematical description of the persistence switch.
Abstract: A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from such persistent bacteria remain sensitive to the antibiotic. We investigated the persistence of single cells of Escherichia coli with the use of microfluidic devices. Persistence was linked to preexisting heterogeneity in bacterial populations because phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates. Quantitative measurements led to a simple mathematical description of the persistence switch. Inherent heterogeneity of bacterial populations may be important in adaptation to fluctuating environments and in the persistence of bacterial infections.
Citations
More filters
Journal ArticleDOI
17 Oct 2008-Cell
TL;DR: Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others, including the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.

2,471 citations


Cites background from "Bacterial Persistence as a Phenotyp..."

  • ...Interestingly, the work of Balaban et al. (2004) showed that a small persistent subpopulation exists even in untreated cultures of E. coli and that these persistent cells are generated continuously during growth....

    [...]

  • ...Interestingly, the work of Balaban et al. (2004) showed that a...

    [...]

Journal ArticleDOI
TL;DR: Stochasticity in gene expression can provide the flexibility needed by cells to adapt to fluctuating environments or respond to sudden stresses, and a mechanism by which population heterogeneity can be established during cellular differentiation and development.
Abstract: Genetically identical cells exposed to the same environmental conditions can show significant variation in molecular content and marked differences in phenotypic characteristics. This variability is linked to stochasticity in gene expression, which is generally viewed as having detrimental effects on cellular function with potential implications for disease. However, stochasticity in gene expression can also be advantageous. It can provide the flexibility needed by cells to adapt to fluctuating environments or respond to sudden stresses, and a mechanism by which population heterogeneity can be established during cellular differentiation and development.

2,381 citations

Journal ArticleDOI
02 Apr 2010-Cell
TL;DR: It is suggested that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.

2,143 citations


Cites background from "Bacterial Persistence as a Phenotyp..."

  • ...This is highly reminiscent of the properties of antibiotic-tolerant bacterial subpopulations, also called ‘‘persisters,’’ which similarly exhibit a transient ability to endure potentially lethal stresses (Balaban et al., 2004; Dhar and McKinney, 2007)....

    [...]

Journal ArticleDOI
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.
Abstract: Biofilms contain bacterial cells that are in a wide range of physiological states. Within a biofilm population, cells with diverse genotypes and phenotypes that express distinct metabolic pathways, stress responses and other specific biological activities are juxtaposed. The mechanisms that contribute to this genetic and physiological heterogeneity include microscale chemical gradients, adaptation to local environmental conditions, stochastic gene expression and the genotypic variation that occurs through mutation and selection. Here, we discuss the processes that generate chemical gradients in biofilms, 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.

1,953 citations


Cites background from "Bacterial Persistence as a Phenotyp..."

  • ...gov/sites/entrez?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=12319"> Escherichia coli at the single-cell leve...

    [...]

Journal ArticleDOI
TL;DR: Global efforts are needed to promote more judicious use of prophylactic antibiotics in aquaculture as accumulating evidence indicates that unrestricted use is detrimental to fish, terrestrial animals, and human health and the environment.
Abstract: Summary The accelerated growth of finfish aquaculture has resulted in a series of developments detrimental to the environment and human health. The latter is illustrated by the widespread and unrestricted use of prophylactic antibiotics in this industry, especially in developing countries, to forestall bacterial infections resulting from sanitary shortcomings in fish rearing. The use of a wide variety of antibiotics in large amounts, including non-biodegradable antibiotics useful in human medicine, ensures that they remain in the aquatic environment, exerting their selective pressure for long periods of time. This process has resulted in the emergence of antibiotic-resistant bacteria in aquaculture environments, in the increase of antibiotic resistance in fish pathogens, in the transfer of these resistance determinants to bacteria of land animals and to human pathogens, and in alterations of the bacterial flora both in sediments and in the water column. The use of large amounts of antibiotics that have to be mixed with fish food also creates problems for industrial health and increases the opportunities for the presence of residual antibiotics in fish meat and fish products. Thus, it appears that global efforts are needed to promote more judicious use of prophylactic antibiotics in aquaculture as accumulating evidence indicates that unrestricted use is detrimental to fish, terrestrial animals, and human health and the environment.

1,947 citations

References
More filters
Journal ArticleDOI
07 Apr 2000-Science
TL;DR: An extension to the soft lithography paradigm, multilayersoft lithography, with which devices consisting of multiple layers may be fabricated from soft materials is described, to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer.
Abstract: Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.

4,218 citations

Journal ArticleDOI
TL;DR: Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes to devices that handle aqueous solutions.
Abstract: Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.

3,344 citations

Journal ArticleDOI
TL;DR: Soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and topattern and manipulate cells.
Abstract: ▪ Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (≥50 μm), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.

2,659 citations

Journal ArticleDOI
TL;DR: The results put clear constraints on the possible molecular mechanisms for the mechanosensory response of focal adhesions to applied force.
Abstract: Mechanical forces play a major role in the regulation of cell adhesion and cytoskeletal organization. In order to explore the molecular mechanism underlying this regulation, we have investigated the relationship between local force applied by the cell to the substrate and the assembly of focal adhesions. A novel approach was developed for real-time, high-resolution measurements of forces applied by cells at single adhesion sites. This method combines micropatterning of elastomer substrates and fluorescence imaging of focal adhesions in live cells expressing GFPtagged vinculin. Local forces are correlated with the orientation, total fluorescence intensity and area of the focal adhesions, indicating a constant stress of 5.5 ± 2 nNμm-2. The dynamics of the force-dependent modulation of focal adhesions were characterized by blocking actomyosin contractility and were found to be on a time scale of seconds. The results put clear constraints on the possible molecular mechanisms for the mechanosensory response of focal adhesions to applied force.

2,161 citations