An Immunohistological Evaluation of Pseudomonas aeruginosa Pulmonary Infection in Two Patients with Cystic Fibrosis

Speert, David P.; Dimmick, James E.; Pier, Gerald B.; Saunders, James; Hancock, Robert E. W.; Kelly, N. M.

doi:10.1203/00006450-198712000-00026

Cited by 28 publications

(12 citation statements)

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“…In addition, the extrapolymeric matrix produced by biofilm bacteria has been shown to inhibit phagocytosis by cells of the immune system (34). Initial microscopic observations of postmortem lung tissue and the sputa of patients suggested that P. aeruginosa forms biofilms in the CF lung (29,48). Recent physiological evidence supports this idea, showing a change in quorumsensing signal profiles comparing free-swimming and biofilm P. aeruginosa organisms (46).…”

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confidence: 61%

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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confidence: 61%

Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

et al. 2001

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“…In this environment, alginate coating has been proposed to play roles in antiphagocytosis (17,41,53) and in biofilm formation (26,54), with the associated phenomena of recalcitrance to antibiotic treatments and resistance to natural clearance mechanisms further compounded by the adhesive properties and viscosity of alginate (41,53). Furthermore, the ability of alginate to afford resistance to oxidants such as hypochlorite and superoxide (27,52), likely to be generated by the numerous neutrophils and monocytes recruited into the inflamed CF lung (41), is considered to be of significance for P. aeruginosa persistence in the respiratory tracts of CF patients.…”

Section: Discussionmentioning

confidence: 99%

Two distinct loci affecting conversion to mucoidy in Pseudomonas aeruginosa in cystic fibrosis encode homologs of the serine protease HtrA

et al. 1996

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Conversion to a mucoid, exopolysaccharide alginate-overproducing phenotype in Pseudomonas aeruginosa is associated with chronic respiratory infections in cystic fibrosis. Mucoidy is caused by muc mutations that derepress the alternative factor AlgU, which in turn activates alginate biosynthetic and ancillary regulatory genes. Here we report the molecular characterization of two newly identified genes, algW and mucD, that affect expression of mucoidy. The algW gene, mapping at 69 min, was isolated on the basis of its ability to suppress mucoidy and reduce transcription of the alginate biosynthetic gene algD. The predicted primary structure of AlgW displayed similarity to HtrA (DegP), a serine protease involved in proteolysis of abnormal proteins and required for resistance to oxidative and heat stress in enteric bacteria. Inactivation of algW on the chromosome of the wild-type nonmucoid strain PAO1 caused increased sensitivity to heat, H 2 O 2 , and paraquat, a redox cycling compound inducing intracellular levels of superoxide. This mutation also permitted significant induction of alginate production in the presence of subinhibitory concentrations of paraquat. Two new genes, mucC and mucD, were identified immediately downstream of the previously characterized portion (algU mucA mucB) of the gene cluster at 67.5 min encoding the alternative factor AlgU and its regulators. Interestingly, the predicted gene product of mucD also showed similarities to HtrA. Inactivation of mucD on the PAO1 chromosome resulted in conversion to the mucoid phenotype. The mutation in mucD also caused increased sensitivity to H 2 O 2 and heat killing. However, in contrast to algW mutants, no increase in susceptibility to paraquat was observed in mucD mutants. These findings indicate that algW and mucD play partially overlapping but distinct roles in P. aeruginosa resistance to reactive oxygen intermediates and heat. In addition, since mutations in mucD and algW cause conversion to mucoidy or lower the threshold for its induction by reactive oxygen intermediates, these factors may repress alginate synthesis either directly by acting on AlgU or its regulators or indirectly by removing physiological signals that may activate this stress response system.Pseudomonas aeruginosa is an opportunistic pathogen causing acute infections in individuals with compromised defense mechanisms, such as burned or neutropenic patients. Another notorious and in many aspects unique infection caused by P. aeruginosa is its characteristic association with the respiratory tract of patients with cystic fibrosis (CF) (8,41,53). This chronic infection differs from the acute disseminated disease by being localized almost exclusively to the lumen of the respiratory tract (1,26,53). Furthermore, the protracted colonization of the respiratory tract is accompanied by a distinct set of phenotypic changes of the bacterium (8, 53). For example, P. aeruginosa strains colonizing CF patients often convert to a mucoid, exopolysaccharide alginate-overproducing phenotype (17), los...

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“…The mucoid phenotype is due to the overproduction of alginate (82), a polymer of ␤-1-4-linked mannuronic acid and guluronic acid (82). P. aeruginosa is believed to form alginate-based biofilms in the CF lung, and this is thought to contribute to the persistence of P. aeruginosa in the CF host (129,182,298). For instance, patients with CF undergo multiple rounds of antibiotic treatment during the course of the disease.…”

Section: Composition Of the Biofilm Matrixmentioning

confidence: 99%

Signals, Regulatory Networks, and Materials That Build and Break Bacterial Biofilms

Karatan

Watnick

2009

Microbiol Mol Biol Rev

866

690

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SUMMARY Biofilms are communities of microorganisms that live attached to surfaces. Biofilm formation has received much attention in the last decade, as it has become clear that virtually all types of bacteria can form biofilms and that this may be the preferred mode of bacterial existence in nature. Our current understanding of biofilm formation is based on numerous studies of myriad bacterial species. Here, we review a portion of this large body of work including the environmental signals and signaling pathways that regulate biofilm formation, the components of the biofilm matrix, and the mechanisms and regulation of biofilm dispersal.

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An Immunohistological Evaluation of Pseudomonas aeruginosa Pulmonary Infection in Two Patients with Cystic Fibrosis

Cited by 28 publications

References 1 publication

Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

Two distinct loci affecting conversion to mucoidy in Pseudomonas aeruginosa in cystic fibrosis encode homologs of the serine protease HtrA

Signals, Regulatory Networks, and Materials That Build and Break Bacterial Biofilms

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