Alginate Inhibition of the Uptake of Pseudomonas aeruginosa by Macrophages

Simpson, Jeremy A.; Smith, Susan E.; Dean, Roger T.

doi:10.1099/00221287-134-1-29

Cited by 97 publications

(93 citation statements)

References 11 publications

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“…AlgT is required for expression of the alginate biosynthetic operon (10,19,31,32). Alginate is thought to have a protective function in a relatively harsh environment in which the bacteria are continually subjected to oxidative stress and attack by the immune system (28,44,45). The switch to mucoidy is also thought to promote persistence of P. aeruginosa in the airways and is usually coincident with a downturn in the prognosis of the patient (27).…”

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Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

et al. 2001

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During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development on an abiotic surface. Biofilms formed by an alginateoverproducing strain exhibit a highly structured architecture and are significantly more resistant to the antibiotic tobramycin than a biofilm formed by an isogenic nonmucoid strain. These results suggest that an important consequence of the conversion to mucoidy is an altered biofilm architecture that shows increasing resistance to antimicrobial treatments.

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Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

et al. 2001

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“…Alginate, composed of a linear copolymer of ␤-D-mannuronic and ␣-L-guluronic acids (17,30,31), confers a selective advantage on P. aeruginosa in the CF patient lung. Alginate insulates the bacterium from killing mechanisms of phagocytes such as hypochlorite (52)(53)(54) and prevents phagocytosis of P. aeruginosa by neutrophils and macrophages (43). Because of the selective advantage that mucoidy confers on P. aeruginosa, the mechanism of alginate production has been studied extensively (26).…”

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Identification of AlgR-Regulated Genes in Pseudomonas aeruginosa by Use of Microarray Analysis

et al. 2004

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The Pseudomonas aeruginosa transcriptional regulator AlgR controls a variety of different processes, including alginate production, type IV pilus function, and virulence, indicating that AlgR plays a pivotal role in the regulation of gene expression. In order to characterize the AlgR regulon, Pseudomonas Affymetrix GeneChips were used to generate the transcriptional profiles of (i) P. aeruginosa PAO1 versus its algR mutant in mid-logarithmic phase, (ii) P. aeruginosa PAO1 versus its algR mutant in stationary growth phase, and (iii) PAO1 versus PAO1 harboring an algR overexpression plasmid. Expression analysis revealed that, during mid-logarithmic growth, AlgR activated the expression of 58 genes while it repressed the expression of 37 others, while during stationary phase, it activated expression of 45 genes and repression of 14 genes. Confirmatory experiments were performed on two genes found to be AlgR repressed (hcnA and PA1557) and one AlgR-activated operon (fimU-pilVWXY1Y2). An S1 nuclease protection assay demonstrated that AlgR repressed both known hcnA promoters in PAO1. Additionally, direct measurement of hydrogen cyanide (HCN) production showed that P. aeruginosa PAO1 produced threefold-less HCN than did its algR deletion strain. AlgR also repressed transcription of two promoters of the uncharacterized open reading frame PA1557. Further, the twitching motility defect of an algR mutant was complemented by the fimTU-pilVWXY1Y2E operon, thus identifying the AlgR-controlled genes responsible for this defect in an algR mutant. This study identified four new roles for AlgR: (i) AlgR can repress gene transcription, (ii) AlgR activates the fimTU-pilVWXY1Y2E operon, (iii) AlgR regulates HCN production, and (iv) AlgR controls transcription of the putative cbb 3 -type cytochrome PA1557.

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“…Following colonization of the CF patient's respiratory tract, mucoid variants of P. aeruginosa emerge, become predominant, and lead to chronic pulmonary disease (32,54). This mucoid phenotype confers an increased capacity to resist phagocytosis (1,66,70) and a mechanism of adherence (39,44,58). P. aeruginosa isolates from non-CF patients rarely show this phenotype, and so the lung environment of the CF patient apparently selects for such mucoid variants.…”

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Posttranslational control of the algT (algU)-encoded sigma22 for expression of the alginate regulon in Pseudomonas aeruginosa and localization of its antagonist proteins MucA and MucB (AlgN)

1997

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Pseudomonas aeruginosa strains associated with cystic fibrosis are often mucoid due to the copious production of alginate, an exopolysaccharide and virulence factor. Alginate gene expression is transcriptionally controlled by a gene cluster at 68 min on the chromosome: algT (algU)-mucA-mucB (algN)-mucC (algM)-mucD (algY). The algT gene encodes a 22-kDa alternative sigma factor ( 22 ) that autoregulates its own promoter (PalgT) as well as the promoters of algR, algB, and algD. The other genes in the algT cluster appear to regulate the expression or activity of 22. The goal of this study was to better understand the functional interactions between 22 and its antagonist regulators during alginate production. Nonmucoid strain PAO1 was made to overproduce alginate (indicating high algD promoter activity) through increasing 22 in the cell by introducing a plasmid clone containing algT from mucA22(Def) strain FRD1. However, the bacterial cells remained nonmucoid if the transcriptionally coupled mucB on the clone remained intact. This suggested that a stoichiometric relationship between 22 and MucB may be required to control sigma factor activity. When the transcription and translational initiation of algT were measured with lacZ fusions, alginate production correlated with only about a 1.2-to 1.7-fold increase in algT-lacZ activity, respectively. An algR-lacZ transcriptional fusion showed a 2.8-fold increase in transcription with alginate production under the same conditions. A Western blot analysis of total cell extracts showed that 22 was approximately 10-fold higher in strains that overproduced alginate, even though algT expression increased less than 2-fold. This suggested that a posttranscriptional mechanism may exist to destabilize 22 in order to control certain 22 -dependent promoters like algD. By Western blotting and phoA fusion analyses, the MucB antagonist of 22 was found to localize to the periplasm of the cell. Similar experiments suggest that MucA localizes to the inner membrane via one transmembrane domain with amino-and carboxy-terminal domains in the cytoplasm and periplasm, respectively. These data were used to propose a model in which MucB-MucA-22 interact via an inner membrane complex that controls the stability of 22 protein in order to control alginate biosynthesis.

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Alginate Inhibition of the Uptake of Pseudomonas aeruginosa by Macrophages

Cited by 97 publications

References 11 publications

Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

Identification of AlgR-Regulated Genes in Pseudomonas aeruginosa by Use of Microarray Analysis

Posttranslational control of the algT (algU)-encoded sigma22 for expression of the alginate regulon in Pseudomonas aeruginosa and localization of its antagonist proteins MucA and MucB (AlgN)

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