<i>Pseudomonas aeruginosa</i>
            LecB Is Involved in Pilus Biogenesis and Protease IV Activity but Not in Adhesion to Respiratory Mucins

Sonawane, Avinash; Jyot, Jeevan; Ramphal, Reuben

doi:10.1128/iai.00551-06

Cited by 28 publications

(40 citation statements)

References 32 publications

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“…In addition, it has been demonstrated that LecA induces a permeability defect in the intestinal epithelium, resulting in increased absorption of exotoxin A, an important extracellular virulence factor (19). Additionally, relationships between lectins and other virulence factors have been shown; for example, LecB was shown to be involved in pilus biogenesis and protease IV activity (29).…”

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confidence: 99%

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

et al. 2009

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Pseudomonas aeruginosa is a frequently encountered pathogen that is involved in acute and chronic lung infections. Lectin-mediated bacterium-cell recognition and adhesion are critical steps in initiating P. aeruginosa pathogenesis. This study was designed to evaluate the contributions of LecA and LecB to the pathogenesis of P. aeruginosa-mediated acute lung injury. Using an in vitro model with A549 cells and an experimental in vivo murine model of acute lung injury, we compared the parental strain to lecA and lecB mutants. The effects of both LecA-and Lec B-specific lectin-inhibiting carbohydrates (␣-methyl-galactoside and ␣-methyl-fucoside, respectively) were evaluated. In vitro, the parental strain was associated with increased cytotoxicity and adhesion on A549 cells compared to the lecA and lecB mutants. In vivo, the P. aeruginosa-induced increase in alveolar barrier permeability was reduced with both mutants. The bacterial burden and dissemination were decreased for both mutants compared with the parental strain. Coadministration of specific lectin inhibitors markedly reduced lung injury and mortality. Our results demonstrate that there is a relationship between lectins and the pathogenicity of P. aeruginosa. Inhibition of the lectins by specific carbohydrates may provide new therapeutic perspectives.

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confidence: 99%

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

et al. 2009

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“…Although this surface localization would perfectly explain the influence of LecB on biofilm formation (50), it is in fact not known at present how the protein traverses the cell envelope, since all secretion signals known in P. aeruginosa are missing (30,50). Furthermore, LecB has been shown to influence type IV pilus formation and the extracellular activity of extracellular protease IV, suggesting that this protein may also affect the type II protein secretion of P. (44). Although the role LecB plays in these processes is completely unknown, this context suggests that LecB might exert its influence in the periplasm, which in turn would require a periplasmic localization of the protein itself.…”

Section: Resultsmentioning

confidence: 99%

Glycosylation Is Required for Outer Membrane Localization of the Lectin LecB inPseudomonas aeruginosa

Bartels¹,

Funken

Knapp

et al. 2011

J Bacteriol

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The fucose-/mannose-specific lectin LecB from Pseudomonas aeruginosa is transported to the outer membrane; however, the mechanism used is not known so far. Here, we report that LecB is present in the periplasm of P. aeruginosa in two variants of different sizes. Both were functional and could be purified by their affinity to mannose. The difference in size was shown by a specific enzyme assay to be a result of N glycosylation, and inactivation of the glycosylation sites was shown by site-directed mutagenesis. Furthermore, we demonstrate that this glycosylation is required for the transport of LecB.Lectins are proteins of nonimmune origin that recognize and bind to specific carbohydrate structural epitopes without modifying them. This group of carbohydrate proteins function as central mediators of information transfer in biological systems and perform their duties by interacting with glycoproteins, glycolipids, and oligosaccharides (34). Lectins exist in a wide range of organisms, including viruses, bacteria, plants, and animals, and are believed to play a general and important role in cell-cell interactions (9). Many bacteria have an arsenal of different lectins for targeting glycosylated proteins of the host (21). One example, the lectin FimH at the top of type 1 pili from the uropathogenic Escherichia coli, recognizes terminally located D-mannose moieties on cell-bound glycoproteins to mediate adhesion between the bacterium and the urothelium (4, 20). Lectins are also of interest for medical and pharmaceutical applications, as exemplified by the galactoside-specific mistletoe lectin, which is widely used as a drug to support anticancer therapy (5).Pseudomonas aeruginosa, an opportunistic pathogen associated with chronic airway infections, synthesizes two lectins, LecA and LecB (formerly also named PA-IL and PA-IIL) (11). Strains of P. aeruginosa which produce high levels of these virulence factors exhibit an increased virulence potential (12). Both lectins play a prominent role in human infection, since it was demonstrated that P. aeruginosa-induced otitis externa diffusa (46), as well as P. aeruginosa in respiratory tract infections (56) and cystic fibrosis patients (16), could successfully be treated by the application of a solution containing specific sugars. The sugar solutions presumably prevented lectin-mediated bacterial adhesion to the corresponding host cells. The expression of lectin genes in P. aeruginosa is coordinately regulated with certain other virulence factors and controlled via the quorum-sensing cascade and by the alternative sigma fac-

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“…Both lectins were proposed to mediate the adhesion of P. aeruginosa to other bacterial cells of the same or different species (14,62), although this role remains debated (56). LecB was shown to be required for posttranscriptional type IV pilus biogenesis, without impairing transcription of pil genes encoding pilus components (56). LecB was therefore necessary for twitching motility, which occurs on solid surfaces or interfaces by extension and retraction of type IV pili (54).…”

Section: Resultsmentioning

confidence: 99%

“…Since single lecA and lecB mutants of PAO1 showed impaired abilities to form biofilms on abiotic surfaces (14,62), the downregulation of lecA and lecB genes in the algU mutant likely contributes to its biofilm formation defect. Both lectins were proposed to mediate the adhesion of P. aeruginosa to other bacterial cells of the same or different species (14,62), although this role remains debated (56). LecB was shown to be required for posttranscriptional type IV pilus biogenesis, without impairing transcription of pil genes encoding pilus components (56).…”

Section: Resultsmentioning

confidence: 99%

The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by NonmucoidPseudomonas aeruginosa

et al. 2010

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The extracytoplasmic function sigma factor AlgU of Pseudomonas aeruginosa is responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. The algU mutant of P. aeruginosa PAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing the algU mutation with a plasmid-borne algU gene restored wild-type phenotypes. Compared with that in PAO1, expression of the psl operon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of the psl operon. Furthermore, expression of the lectin-encoding lecA and lecB genes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes, but AlgU is involved in the expression of the ppyR gene, whose product was reported to positively control psl expression. Expressing the ppyR gene in PAOU partially restored the formation of robust biofilms.

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Pseudomonas aeruginosa LecB Is Involved in Pilus Biogenesis and Protease IV Activity but Not in Adhesion to Respiratory Mucins

Cited by 28 publications

References 32 publications

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

Role of LecA and LecB Lectins in Pseudomonas aeruginosa -Induced Lung Injury and Effect of Carbohydrate Ligands

Glycosylation Is Required for Outer Membrane Localization of the Lectin LecB inPseudomonas aeruginosa

The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by NonmucoidPseudomonas aeruginosa

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