Conversion of Pseudomonas aeruginosa to mucoidy in cystic fibrosis: environmental stress and regulation of bacterial virulence by alternative sigma factors

Deretić, Vojo; Schurr, Michael J.; Boucher, J C; Martin, Daniel W.

doi:10.1128/jb.176.10.2773-2780.1994

Cited by 205 publications

(206 citation statements)

References 78 publications

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“…As a consequence, studies on the regulation of alginate production have been carried out largely in variants selected for the stable expression of mucoidy (3,19,30,32). Such variants have been subsequently shown to contain mutations in the anti-sigma factors algN or mucA (which suppress the sigma factor AlgU) and thus result in upregulation of AlgU activity (2,3,33). Mucoidy can also be induced by increasing algU gene dosage by transformation with a multicopy plasmid containing this gene (33), presumably due to increased levels of AlgU.…”

Section: Resultsmentioning

confidence: 99%

“…They include the response regulators AlgR and AlgB; the alternative sigma factor AlgU (or AlgT), which is required for the transcription of alginate biosynthetic genes; the anti-sigma factors MucA and AlgN (or MucB), which counteract the function of AlgU; the histone-like protein AlgP; and AlgQ, the exact function of which is unclear (2,3). AlgR and AlgB have been the subject of considerable study and appear to represent the receiver components of classical sensor-regulator pairs, but their cognate sensors have not been identified.…”

mentioning

confidence: 99%

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The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

Whitchurch

Alm

Mattick

1996

Proc. Natl. Acad. Sci. U.S.A.

133

152

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Mucoid strains of Pseudomonas aeruginosa isolated from the lungs of cystic fibrosis patients produce large amounts of the exopolysaccharide alginate. AlgR has long been considered a key regulator of alginate production, but its cognate sensor has not been identified. Here we show that AlgR is required for twitching motility, which is a form ofbacterial surface translocation mediated by type 4 fimbriae. Adjacent to algR we have identified a sensor gene (fimS), which is also required for twitching motility. However, FimS does not appear to be required for alginate production in mucoid strains. FimS and AlgR are representative of a new subclass of two-component transmitter-receiver regulatory systems. The alternative sigma factor AlgU also affects both alginate production and twitching motility. Therefore, these two virulence determinants appear to be closely associated and coordinately regulated.Pseudomonas aeruginosa is an opportunistic pathogen of humans and other species (1). It causes severe chronic infections in patients who are immunocompromised as a result of cancer chemotherapy or AIDS, or who are suffering from burns or cystic fibrosis. It produces an extensive suite of virulence factors including extracellular proteases and toxins, lipases, pyochelins, exopolysaccharides, and type 4 fimbriae. In cystic fibrosis, P. aeruginosa produces recurrent and chronic lung infections, which impose substantial morbidity and often mortality as a consequence of accumulated damage to the lung. Isolates from such chronic infections exhibit a "mucoid" colony phenotype due to the production of large amounts of the exopolysaccharide alginate, apparently as a means of evading immune responses (for reviews see refs. 2 and 3).

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

Whitchurch

Alm

Mattick

1996

Proc. Natl. Acad. Sci. U.S.A.

133

152

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“…The clinical relevance of P. aeruginosa is largely known as it is an important human opportunistic pathogen, frequently involved in severe and often fatal infections in patients with cystic fibrosis (CF) and other immunodepressive illnesses (Govan & Deretic, 1996;van Delden & Iglewski, 1998). An interesting observation is that, particularly from CF patients, P. aeruginosa isolates display significant phenotypic variation, such as a wide spectrum of colony variants, development of mucoid phenotype and highly adherent small-colony variants, absence of cell motility, development of variants resistant to macrophage phagocytosis and acquisition of resistance to multiple antibiotics (Deretic et al, 1994;Govan & Deretic, 1996;Mahenthiralingam et al, 1994;Oliver et al, 2000;Häußler et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Emergence of phenotypic variants upon mismatch repair disruption in Pseudomonas aeruginosa

et al. 2004

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MutS is part of the bacterial mismatch repair system that corrects point mutations and small insertions/deletions that fail to be proof-read by DNA polymerase activity. In this work it is shown that the disruption of the P. aeruginosa mutS gene generates the emergence of diverse colony morphologies in contrast with its parental wild-type strain that displayed monomorphic colonies. Interestingly, two of the mutS morphotypes emerged at a high frequency and in a reproducible way and were selected for subsequent characterization. One of them displayed a nearly wild-type morphology while the other notably showed, compared with the wild-type strain, increased production of pyocyanin and pyoverdin, lower excretion of LasB protease and novel motility characteristics, mainly related to swarming. Furthermore, it was reproducibly observed that, after prolonged incubation in liquid culture, the pigmented variant consistently emerged from the mutS wild-type-like variant displaying a reproducible event. It is also shown that these P. aeruginosa mutS morphotypes not only displayed an increase in the frequency of antibiotic-resistant mutants, as described for clinical P. aeruginosa mutator isolates, but also generated mutants whose antibiotic-resistant levels were higher than those measured from spontaneous resistant mutants derived from wild-type cells. It was also found that both morphotypes showed a decreased cytotoxic capacity compared to the wild-type strain, leading to the emergence of invasive variants. By using mutated versions of a tetracycline resistance gene, the mutS mutant showed a 70-fold increase in the reversion frequency of a +1 frameshift mutation with respect to its parental wild-type strain, allowing the suggestion that the phenotypical diversity generated in the mutS population could be produced in part by frameshift mutations. Finally, since morphotypical diversification has also been described in clinical isolates, the possibility that this mutS diversification was related to the high frequency hypermutability observed in P. aeruginosa CF isolates is discussed.

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“…Many responses involve regulation of sets of genes (Brown et al 1990). From many studies, one can predict that biofilm bacteria will differ from their planktonic counterparts at the level of genetic regulation and thus may differ profoundly in many a physiological change inherent to surface-associated growth did not, either fortuitously or by design, affect their susceptibility to antimicrobial agents (Deretic et al 1994). …”

Section: Physiological Traits Of Biofilm Bacteria Which May Bestow Rmentioning

confidence: 99%

Effect of Metallic Implant on the Risk of Bacterial Osteomyelitis in Small Animals

Soontornvipart¹,

Nečas²,

Dvořák³

2003

Acta Vet. Brno

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Metallic implants are frequently used for stabilization of fractures in dogs and cats. Postoperative bacterial osteomyelitis is a recognized complication following fracture repair and can be influenced by the presence of metallic implants. Metallic implants influence susceptibility to infection through several mechanisms, including corrosion, adherence of biofilm, isolation from the immune response, and compromise of blood supply. Factors that should be considered when using metallic implants include antibiotic prophylaxis, appropriate implant selection, meticulous surgical technique and proper aseptic technique.

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Conversion of Pseudomonas aeruginosa to mucoidy in cystic fibrosis: environmental stress and regulation of bacterial virulence by alternative sigma factors

Cited by 205 publications

References 78 publications

The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa.

Emergence of phenotypic variants upon mismatch repair disruption in Pseudomonas aeruginosa

Effect of Metallic Implant on the Risk of Bacterial Osteomyelitis in Small Animals

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