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Journal ArticleDOI

Pseudomonas aeruginosa: all roads lead to resistance.

TL;DR: Very large collections of genes (the resistome) that when mutated lead to resistance as well as new forms of adaptive resistance that can be triggered by antibiotics themselves, in in vivo growth conditions or complex adaptations such as biofilm growth or swarming motility are identified.
About: This article is published in Trends in Microbiology.The article was published on 2011-08-01. It has received 958 citations till now. The article focuses on the topics: Resistome & Pseudomonas aeruginosa.
Citations
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Journal ArticleDOI
TL;DR: An overview of the host response and how the genomic capacity of P. aeruginosa contributes to the pathogenesis and persistence of these infections is provided.
Abstract: Pseudomonas aeruginosa is a metabolically versatile bacterium that can cause a wide range of severe opportunistic infections in patients with serious underlying medical conditions. These infections are characterized by an intense neutrophilic response resulting in significant damage to host tissues and often exhibit resistance to antibiotics leading to mortality. Treatment of persistent infections is additionally hampered by adaptive resistance, due to the growth state of the bacterium in the patient including the microorganism's ability to grow as a biofilm. An array of P. aeruginosa virulence factors counteract host defences and can cause direct damage to host tissues or increase the bacterium's competitiveness. New prevention and treatment methods are urgently required to improve the outcome of patients with P. aeruginosa infections. This review describes the two main types of P. aeruginosa lung infections and provides an overview of the host response and how the genomic capacity of P. aeruginosa contributes to the pathogenesis and persistence of these infections.

1,032 citations

Journal ArticleDOI
TL;DR: The mechanism of antibiotic resistance in P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections.

908 citations

Journal ArticleDOI
TL;DR: Novel strategies that specifically target the biofilm mode of growth have been recently described, thus providing the basis for future anti-biofilm therapy.

626 citations

Journal ArticleDOI
TL;DR: Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging.

534 citations


Cites background from "Pseudomonas aeruginosa: all roads l..."

  • ...Given that CF patients are subjected to prolonged and often intensive therapy with antibiotics [18], the evolution of antibiotic resistances is also a common adaptation [19]....

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Journal ArticleDOI
TL;DR: The development and application of flavonoid-based drugs could be a promising approach for antibiotic-resistant infections and improve understanding of the biological and molecular roles of plant flavonoids, focusing mostly on their antimicrobial activities.
Abstract: Flavonoids are one of the largest classes of small molecular secondary metabolites produced in different parts of the plant. They display a wide range of pharmacological and beneficial health effects for humans, which include, among others, antioxidative activity, free radical scavenging capacity, coronary heart disease prevention and antiatherosclerotic, hepatoprotective, anti-inflammatory, and anticancer activities. Hence, flavonoids are gaining high attention from the pharmaceutical and healthcare industries. Notably, plants synthesize flavonoids in response to microbial infection, and these compounds have been found to be a potent antimicrobial agent against a wide range of pathogenic microorganisms in vitro. Antimicrobial action of flavonoids results from their various biological activities, which may not seem very specific at first. There are, however, promising antibacterial flavonoids that are able not only to selectively target bacterial cells, but also to inhibit virulence factors, as well as other forms of microbial threats, e.g. biofilm formation. Moreover, some plant flavonoids manifest ability to reverse the antibiotic resistance and enhance action of the current antibiotic drugs. Hence, the development and application of flavonoid-based drugs could be a promising approach for antibiotic-resistant infections. This review aims to improve our understanding of the biological and molecular roles of plant flavonoids, focusing mostly on their antimicrobial activities.

464 citations

References
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Journal ArticleDOI
21 May 1999-Science
TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
Abstract: Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.

11,162 citations

Book
01 Apr 2006
TL;DR: Advances in understanding and treatment of cystic fibrosis are summarized, focusing on pulmonary disease, which accounts for most morbidity and deaths.
Abstract: Cystic fibrosis is the most common autosomal recessive disorder in white people, with a frequency of about 1 in 2500 livebirths. Discovery of the mutated gene encoding a defective chloride channel in epithelial cells--named cystic fibrosis transmembrane conductance regulator (CFTR)--has improved our understanding of the disorder's pathophysiology and has aided diagnosis, but has shown the disease's complexity. Gene replacement therapy is still far from being used in patients with cystic fibrosis, mostly because of difficulties of targeting the appropriate cells. Life expectancy of patients with the disorder has been greatly increased over past decades because of better notions of symptomatic treatment strategies. Here, we summarise advances in understanding and treatment of cystic fibrosis, focusing on pulmonary disease, which accounts for most morbidity and deaths.

4,585 citations

Journal ArticleDOI
31 Aug 2000-Nature
TL;DR: It is proposed that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances.
Abstract: Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances.

4,220 citations

Journal ArticleDOI
TL;DR: The isolation and characterization of mutants of Pseudomonas aeruginosa PA14 defective in the initiation of biofilm formation on an abiotic surface, polyvinylchloride (PVC) plastic are reported and evidence that microcolonies form by aggregation of cells present in the monolayer is presented.
Abstract: The formation of complex bacterial communities known as biofilms begins with the interaction of planktonic cells with a surface in response to appropriate environmental signals. We report the isolation and characterization of mutants of Pseudomonas aeruginosa PA14 defective in the initiation of biofilm formation on an abiotic surface, polyvinylchloride (PVC) plastic. These mutants are designated surface attachment defective (sad ). Two classes of sad mutants were analysed: (i) mutants defective in flagellar-mediated motility and (ii) mutants defective in biogenesis of the polar-localized type IV pili. We followed the development of the biofilm formed by the wild type over 8 h using phase-contrast microscopy. The wild-type strain first formed a monolayer of cells on the abiotic surface, followed by the appearance of microcolonies that were dispersed throughout the monolayer of cells. Using time-lapse microscopy, we present evidence that microcolonies form by aggregation of cells present in the monolayer. As observed with the wild type, strains with mutations in genes required for the synthesis of type IV pili formed a monolayer of cells on the PVC plastic. However, in contrast to the wild-type strain, the type IV pili mutants did not develop microcolonies over the course of the experiments, suggesting that these structures play an important role in microcolony formation. Very few cells of a non-motile strain (carrying a mutation in flgK) attached to PVC even after 8 h of incubation, suggesting a role for flagella and/or motility in the initial cell-to-surface interactions. The phenotype of these mutants thus allows us to initiate the dissection of the developmental pathway leading to biofilm formation.

2,712 citations

Journal ArticleDOI
TL;DR: Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy and a promising strategy may be the use of enzymes that can dissolve the biofilm matrix as well as quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics.

2,637 citations

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