Molecular Modifications of the Pseudomonas Quinolone Signal in the Intermicrobial Competition with Aspergillus

The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule for Pseudomonas aeruginosa that regulates virulence factors, chelates iron, and is an important factor in interactions with eukaryotes, including fungi and mammalian hosts. It was previously shown to inhibit or boost Aspergillus, depending on the milieu iron concentration. We studied several molecular modifications of the PQS molecule, and their effects on Aspergillus biofilm metabolism and growth in vitro, and the effects of iron supplementation. We found that most molecules inhibited Aspergillus at concentrations similar to that of PQS, but with relatively flat dose-responses, and all were less potent than PQS. The inhibition was reversible by iron, suggesting interference with fungal iron metabolism. Stimulation of Aspergillus was not noted. We conclude that the critical Aspergillus-inhibiting moeities of the PQS molecule were partially, but not completely, interfered with by molecular modifications at several sites on the PQS molecule. The mechanism, as with PQS, appears to relate to fungal iron metabolism.

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Comparison between Pseudomonas aeruginosa siderophores and desferrioxamine for iron acquisition from ferritin

Asian Biomedicine ◽

10.2478/abm-2010-0080 ◽

2010 ◽

Vol 4 (4) ◽

pp. 631-635 ◽

Cited By ~ 3

Author(s):

Somporn Srifuengfung ◽

Susan Assanasen ◽

Malulee Tuntawiroon ◽

Sumonrat Meejanpetch

Keyword(s):

Pseudomonas Aeruginosa ◽

Iron Acquisition ◽

Iron Chelator ◽

Dialysis Membrane ◽

In Vitro Experiment ◽

Iron Mobilization ◽

Ph Values ◽

Minimum Medium ◽

Stimulation Of

Abstract Background: Siderophore is an iron chelator produced by microorganism. Pseudomonas aeruginosa produces two siderophores (pyoverdin and pyochelin). Desferrioxamine is a siderophore used in thalassemia patients to treat an iron overload of vital organs. Objective: Compare the ability of pyoverdin, pyochelin, and desferrioxamine for iron mobilization from ferritin. Materials and Methods: In vitro experiment, the ability of P. aeruginosa siderophores and desferrioxamine for iron mobilization from ferritin was compared by using a dialysis membrane assay at pH values of 7.4 and 6.0. Stimulation of P. aeruginosa PAO1 growth by all siderophores was studied in glucose minimum medium. Results: All three compounds were capable of iron mobilization at both pHs. At pH 6.0, the most effectiveness compound was desferrioxamine (31.6%), followed by pyoverdin (21.5%) and pyochelin (13.7%) compared on weight basis, each at 10 μg/mL. At equimolar concentration, their activities were desferrioxamine (38.5±1.2%), followed by pyoverdin (32.0±4.8%) and pyochelin (26.7±1.9%), respectively. Conclusion: The most effective compound in iron mobilization from ferritin was desferrioxamine, followed by pyoverdin and pyochelin respectively.

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A Survival Strategy for Pseudomonas aeruginosa That Uses Exopolysaccharides To Sequester and Store Iron To Stimulate Psl-Dependent Biofilm Formation

Applied and Environmental Microbiology ◽

10.1128/aem.01307-16 ◽

2016 ◽

Vol 82 (21) ◽

pp. 6403-6413 ◽

Cited By ~ 20

Author(s):

Shan Yu ◽

Qing Wei ◽

Tianhu Zhao ◽

Yuan Guo ◽

Luyan Z. Ma

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Iron Concentration ◽

Survival Strategy ◽

Iron Storage ◽

Content Type ◽

High Level ◽

Biofilm Development ◽

Biofilm Matrix

ABSTRACTExopolysaccharide Psl is a critical biofilm matrix component inPseudomonas aeruginosa, which forms a fiber-like matrix to enmesh bacterial communities. Iron is important forP. aeruginosabiofilm development, yet it is not clearly understood how iron contributes to biofilm development. Here, we showed that iron promoted biofilm formation via elevating Psl production inP. aeruginosa. The high level of iron stimulated the synthesis of Psl by reducing rhamnolipid biosynthesis and inhibiting the expression of AmrZ, a repressor ofpslgenes. Iron-stimulated Psl biosynthesis and biofilm formation held true in mucoidP. aeruginosastrains. Subsequent experiments indicated that iron bound with Pslin vitroand in biofilms, which suggested that Psl fibers functioned as an iron storage channel inP. aeruginosabiofilms. Moreover, among three matrix exopolysaccharides ofP. aeruginosa, Psl is the only exopolysaccharide that can bind with both ferrous and ferric ion, yet with higher affinity for ferrous iron. Our data suggest a survival strategy ofP. aeruginosathat uses exopolysaccharide to sequester and store iron to stimulate Psl-dependent biofilm formation.IMPORTANCEPseudomonas aeruginosais an environmental microorganism which is also an opportunistic pathogen that can cause severe infections in immunocompromised individuals. It is the predominant airway pathogen causing morbidity and mortality in individuals affected by the genetic disease cystic fibrosis (CF). Increased airway iron and biofilm formation have been proposed to be the potential factors involved in the persistence ofP. aeruginosain CF patients. Here, we showed that a high level of iron enhanced the production of the key biofilm matrix exopolysaccharide Psl to stimulate Psl-dependent biofilm formation. Our results not only make the link between biofilm formation and iron concentration in CF, but also could guide the administration or use of iron chelators to interfere with biofilm formation inP. aeruginosain CF patients. Furthermore, our data also imply a survival strategy ofP. aeruginosaunder high-iron environmental conditions.

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Modification of In Vivo and In Vitro T- and B-Cell-Mediated Immune Responses by the Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-Oxododecanoyl)-l-Homoserine Lactone

Infection and Immunity ◽

10.1128/iai.71.8.4421-4431.2003 ◽

2003 ◽

Vol 71 (8) ◽

pp. 4421-4431 ◽

Cited By ~ 76

Author(s):

Adam J. Ritchie ◽

Andrew O. W. Yam ◽

Kara M. Tanabe ◽

Scott A. Rice ◽

Margaret A. Cooley

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Immune Responses ◽

Cytokine Production ◽

Homoserine Lactone ◽

Relative Increase ◽

Ifn Γ ◽

Quorum Sensing Molecule

ABSTRACT N-3-(oxododecanoyl)-l-homoserine lactone (OdDHL), a quorum-sensing molecule of Pseudomonas aeruginosa, plays an important role in the pathogenesis of the organism through its control of virulence factor expression. Several reports have suggested that OdDHL can also directly modulate host immune responses. However, the nature of the modulation is controversial, with different reports suggesting promotion of either humoral (Th2-mediated) or inflammatory (Th1-mediated) responses. This report describes a series of studies which demonstrate for the first time that in vivo administration of OdDHL can modulate the course of an antibody response, with an increase in ovalbumin (OVA)-specific immunogloblulin G1 (IgG1) but not IgG2a in OdDHL-treated OVA-immunized BALB/c mice compared to levels for controls. In vitro stimulation of lymphocytes from both Th1-biased C57Bl/6 and T-cell receptor transgenic mice and Th2-biased BALB/c mice in the presence of OdDHL demonstrated that OdDHL inhibits in vitro cytokine production in response to both mitogen and antigen, with gamma interferon (IFN-γ) tending to be more inhibited than interleukin-4 (IL-4). In vitro mitogen or antigen restimulation of cells from mice treated with OdDHL in vivo shows effects on cytokine production which depend on the underlying immune bias of the mouse strain used, with a relative increase of IFN-γ in Th1-biased C57Bl/6 mice and a relative increase of IL-4 in Th2-biased BALB/c mice. Thus, the mode of action of OdDHL on T-cell cytokine production is likely to be a relatively nonspecific one which accentuates an underlying immune response bias rather than one which specifically targets either Th1 or Th2 responses.

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Stimulation of innate immunity by susceptible and multidrug-resistant Pseudomonas aeruginosa: an in vitro and in vivo study

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.2003.02365.x ◽

2004 ◽

Vol 135 (2) ◽

pp. 240-246 ◽

Cited By ~ 27

Author(s):

E. J. GIAMARELLOS-BOURBOULIS ◽

D. PLACHOURAS ◽

A. TZIVRA ◽

V. KOUSOULAS ◽

N. BOLANOS ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Innate Immunity ◽

Multidrug Resistant ◽

In Vivo Study ◽

Stimulation Of

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Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus response to iron

Microbiology ◽

10.1099/mic.0.000858 ◽

2020 ◽

Vol 166 (1) ◽

pp. 44-55 ◽

Cited By ~ 8

Author(s):

Hasan Nazik ◽

Gabriele Sass ◽

Shajia R. Ansari ◽

Reyhan Ertekin ◽

Hubertus Haas ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Aspergillus Fumigatus ◽

Biofilm Formation ◽

Fungal Growth ◽

Wild Type ◽

Content Type ◽

Pseudomonas Quinolone Signal ◽

Maximal Stimulation ◽

Fe Homeostasis ◽

Quorum Sensing Molecule

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af), the commonest bacterium and fungus in compromised host airways, compete for iron (Fe). The Pseudomonas quinolone signal (PQS), a Pa quorum sensing molecule, also chelates Fe, and delivers Fe to the Pa cell membrane using Pa siderophores. In models of Af biofilm formation or preformed biofilms, PQS inhibited Af in a low Fe environment. AfΔsidA (mutant unable to produce siderophores) biofilm was more sensitive to PQS inhibition than wild-type (WT), as was planktonic AfΔsidA growth. PQS decreased WT Af growth on agar. All these inhibitory actions were reversed by Fe. The Pa siderophore pyoverdin, or Af siderophore inhibitor celastrol, act cooperatively with PQS in Af inhibition. These findings all indicate PQS inhibition is owing to Fe chelation. Remarkably, in high Fe environments, PQS enhanced Af biofilm at 1/100 to 1/2000 Fe concentration required for Fe alone to enhance. Planktonic Af growth, and on agar, Af conidiation, were also enhanced by PQS+Fe compared to Fe alone. In contrast, neither AfΔsidA biofilm, nor planktonic AfΔsidA, were enhanced by PQS-Fe compared to Fe. When Af siderophore ferricrocin (FC),+PQS, were added to AfΔsidA, Af was then boosted more than by FC alone. Moreover, FC+PQS+Fe boosted AfΔsidA more than Fe, FC, FC+Fe, PQS+FC or PQS+Fe. Thus PQS-Fe maximal stimulation requires Af siderophores. PQS inhibits Af via chelation under low Fe conditions. In a high Fe environment, PQS paradoxically stimulates Af efficiently, and this involves Af siderophores. PQS production by Pa could stimulate Af in cystic fibrosis airways, where Fe homeostasis is altered and Fe levels increase, supporting fungal growth.

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Early Platelet-Collagen Interactions in Whole Blood and Their Modifications by Aspirin and Dipyridamole Evaluated by a New Method (Basic Wave)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660136 ◽

1985 ◽

Vol 54 (04) ◽

pp. 799-803 ◽

Cited By ~ 14

Author(s):

José Luís Pérez-Requejo ◽

Justo Aznar ◽

M Teresa Santos ◽

Juana Vallés

Keyword(s):

Whole Blood ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

White Blood Cells ◽

Reversible Aggregation ◽

Inhibitory Compounds ◽

Rapid Generation ◽

Stimulation Of ◽

Collagen Stimulation

SummaryIt is shown that the supernatant of unstirred whole blood at 37° C, stimulated by 1 μg/ml of collagen for 10 sec, produces a rapid generation of pro and antiaggregatory compounds with a final proaggregatory activity which can be detected for more than 60 min on a platelet rich plasma (PRP) by turbidometric aggregometry. A reversible aggregation wave that we have called BASIC wave (for Blood Aggregation Stimulatory and Inhibitory Compounds) is recorded. The collagen stimulation of unstirred PRP produces a similar but smaller BASIC wave. BASIC’s intensity increases if erythrocytes are added to PRP but decreases if white blood cells are added instead. Aspirin abolishes “ex vivo” the ability of whole blood and PRP to generate BASIC waves and dipyridamole “in vitro” significantly reduces BASIC’s intensity in whole blood in every tested sample, but shows little effect in PRP.

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DER EINFLUSS VON RESERPIN AUF DIE ANTITHYREOIDALE WIRKUNG VON KALIUMPERCHLORAT

Acta Endocrinologica ◽

10.1530/acta.0.0390423 ◽

1962 ◽

Vol 39 (3) ◽

pp. 423-430

Author(s):

H. L. Krüskemper ◽

F. J. Kessler ◽

E. Steinkrüger

Keyword(s):

Thyroid Gland ◽

Male Rats ◽

Normal Male ◽

Tissue Respiration ◽

List Type ◽

Morphological Alterations ◽

Hormone Synthesis ◽

Stimulation Of

ABSTRACT 1. Reserpine does not inhibit the tissue respiration of liver in normal male rats (in vitro). 2. The decrease of tissue respiration of the liver with simultaneous morphological stimulation of the thyroid gland after long administration of reserpine is due to a minute inhibition of the hormone synthesis in the thyroid gland. 3. The morphological alterations of the thyroid in experimental hypothyroidism due to perchlorate can not be prevented with reserpine.

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EFFECT OF ACTINOMYCIN D ON TSH-INDUCED STIMULATION OF THYROIDAL PROTEIN SYNTHESIS IN THE RAT

Acta Endocrinologica ◽

10.1530/acta.0.0770064 ◽

1974 ◽

Vol 77 (1) ◽

pp. 64-70 ◽

Cited By ~ 9

Author(s):

Gustav Wägar

Keyword(s):

Protein Synthesis ◽

Actinomycin D ◽

The Other ◽

Leucine Incorporation ◽

Short Term ◽

Other Hand ◽

Thyroid Glands ◽

Translational Level ◽

Stimulation Of

ABSTRACT Whether the short-term regulation of thyroidal protein synthesis by TSH occurs at the transcriptional or the translational level was tested by measuring the effect of actinomycin D (act D) on the TSH-induced stimulation of L-14C-leucine incorporation into the thyroidal proteins of rats. TSH was injected 6 h before the rats were killed. The thyroid glands were then removed and incubated in vitro in the presence of L-14C-leucine for 2 h. The pronounced stimulation of leucine incorporation in the TSH-treated animals was depressed as compared with controls but still significant even when the animals had been pre-treated with 100 μg act D 24 and 7 h before sacrifice. On the other hand, act D strongly decreased incorporation of 3H-uridine into RNA. Short-term regulation of thyroidal protein synthesis by TSH appears to be partly but not wholly dependent on neosynthesis of RNA. Hence regulation may partly occur at the translation level of protein synthesis.

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