Siderophore‐mediated cell signalling in <i>Pseudomonas aeruginosa</i>: divergent pathways regulate virulence factor production and siderophore receptor synthesis

Beare, Paul A.; For, Raewyn J.; Martin, Lois W.; Lamont, Iain L.

doi:10.1046/j.1365-2958.2003.03288.x

Cited by 191 publications

(214 citation statements)

References 61 publications

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“…Upon binding to iron, the Fe-PVD-FpvA complex interacts with the periplasmic domain of FpvR, allowing the expression of the regulators PvdS (PA2426) and FpvI (PA2387). PvdS upregulates the production of ToxA, PrpL, and pyoverdine, whereas expression of FpvI generates a positive-feedback loop through increased production of the PVD receptor FpvA (9). Recently, Shirley and Lamont characterized an additional protein necessary for the transport and signaling cascade of Fe-PVD (178).…”

Section: Pyoverdinementioning

confidence: 99%

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

Nadal‐Jimenez

Koch

Thompson

et al. 2012

Microbiol Mol Biol Rev

629

626

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SUMMARY Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In several pathogens, this process triggers the production of virulence factors and/or a switch in bacterial lifestyle that is a major determining factor in the outcome and severity of the infection. Understanding how bacteria control these signaling systems is crucial to the development of novel antimicrobial agents capable of reducing virulence while allowing the immune system of the host to clear bacterial infection, an approach likely to reduce the selective pressures for development of resistance. We provide here an up-to-date overview of the molecular basis and physiological implications of cell-to-cell signaling systems in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas aeruginosa . All of the known cell-to-cell signaling systems in this bacterium are described, from the most-studied systems, i.e., N -acyl homoserine lactones (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), to less-well-studied signaling molecules, including diketopiperazines, fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and pyocyanin. This overview clearly illustrates that bacterial communication is far more complex than initially thought and delivers a clear distinction between signals that are quorum sensing dependent and those relying on alternative factors for their production.

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Section: Pyoverdinementioning

confidence: 99%

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

Nadal‐Jimenez

Koch

Thompson

et al. 2012

Microbiol Mol Biol Rev

629

626

View full text Add to dashboard Cite

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“…Up-and downregulation of extracellular enzymes by iron limitation has been described for different bacteria (Tokuda et al, 1998;Enard & Expert, 2000;Maunsell et al, 2006). Although in some cases this regulation is part of a more complex pathway related to virulence (Beare et al, 2003), the function of this association remains unclear. F. psychrophilum is able to degrade haemoglobin (Nematollahi et al, 2003); thus the production of certain proteases related to haemolysis could perhaps be regulated by the levels of iron.…”

Section: Phenotypic Characterization Of the Fp1033 Mutantmentioning

confidence: 99%

A mutant in one of two exbD loci of a TonB system in Flavobacterium psychrophilum shows attenuated virulence and confers protection against cold water disease

Álvarez

Menéndez

et al. 2008

Microbiology

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Flavobacterium psychrophilum is a psychrotrophic fish-pathogenic bacterium that causes cold water disease (CWD) in salmonids. By means of Tn4351 mutagenesis a mutant named FP1033, deficient in growth on iron-depleted medium, was previously isolated. FP1033 recovered the parental phenotype in the presence of iron. The gene disrupted by the transposon in this mutant encoded a protein with similarity to ExbD proteins, which are members of the TonB complex system involved in iron uptake mediated by siderophores. Analysis of the DNA surrounding the transposon insertion showed the presence of a tonB cluster of genes composed of exbB, two exbD (exbD1 and exbD2) and tonB loci. RT-PCR analysis and complementation studies indicated that these genes are transcribed as an operon and that the exbD2 : : Tn4351 phenotype was caused by the lack of ExbD2. FP1033 showed decreased virulence and conferred a high level of protection in rainbow trout fry after vaccination. This is believed to be the first report of a F. psychrophilum attenuated strain that induces a protective immune response in rainbow trout against CWD. These results suggest that the exbD2 locus from this particular TonB system is a suitable target to generate a live attenuated vaccine.

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“…Sequence analysis of ORF BPSL1787 revealed that it encodes a predicted protein with similarity to PvdS, an ECF sigma factor from P. aeruginosa (AAB09714; 44% I, 60% S) (16). PvdS is involved in the transcriptional activation of the pyoverdin biosynthesis genes, as well as other genes encoding virulence factors such as the endoprotease PrpL and exotoxin A (4,26,38,39,67). We designated this gene mbaS (for malleobactin sigma factor).…”

Section: Vol 188 2006 Siderophore Synthesis and Transport In B Psementioning

confidence: 99%

Genetic and Transcriptional Analysis of the Siderophore Malleobactin Biosynthesis and Transport Genes in the Human Pathogen Burkholderia pseudomallei K96243

et al. 2006

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Burkholderia pseudomallei is a gram-negative facultative intracellular pathogen that causes melioidosis, an invasive disease of humans and animals. To address the response of this bacterium to iron-limiting conditions, we first performed a global transcriptional analysis of RNA extracted from bacteria grown under iron-limiting and iron-rich conditions by microarrays. We focused our study on those open reading frames (ORFs) induced under iron limitation, which encoded predicted proteins that could be involved in the biosynthesis and uptake of the siderophore malleobactin. We purified this siderophore and determined that it consisted of at least three compounds with different molecular weights. We demonstrated that ORFs BPSL1776 and BPSL1774, designated mbaA and mbaF, respectively, are involved in the biosynthesis of malleobactin, while BPSL1775, named fmtA, is involved in its transport. These genes are in an operon with two other ORFs (mbaJ and mbaI) whose transcription is under the control of MbaS, a protein that belongs to the extracytoplasmic function sigma factors. Interestingly, the transcription of the mbaA, fmtA, and mbaS genes is not controlled by the availability of the siderophore malleobactin.Burkholderia pseudomallei is a gram-negative facultative intracellular pathogen that is the causative agent of melioidosis. Although this invasive disease is endemic to southeast Asia and northern Australia, its worldwide availability, high rate of mortality, and aerosol infectivity resulted in its classification as a select agent (12, 65). B. pseudomallei is also a saprophytic organism that has developed high resistance to many hostile environmental conditions such as acidic environments, dehydration, prolonged nutrient starvation, and antiseptic and detergent solutions (12).Despite increasing knowledge on the epidemiology of this disease, very little is known on the molecular mechanisms of the infection; only a few virulence factors, i.e., the capsular polysaccharide, lipopolysaccharide, type IV pilus, and a type III secretion apparatus, have been described with animal models (55,64). This pathogen can invade phagocytic and nonphagocytic cells using the type III secretion apparatus to promote its escape into the cytoplasm, where the bacterium induces polar actin polymerization (56, 57). Intracellular B. pseudomallei cells can induce host cell membrane protrusions that may facilitate cell-to-cell spread of the bacteria and induce the fusion of adjacent cells forming giant multinucleated cells (24,25,54). Sequencing of the two B. pseudomallei chromosomes (22) has generated a significant amount of data expected to yield information on new virulence factors and putative targets for vaccine development.A potential virulence factor in B. pseudomallei that so far has not been studied is the ability to utilize iron, a feature that may play an important role in the pathogenesis of the disease caused by this bacterium. Iron is required for the growth of nearly all microorganisms in the environment, as well as in biologica...

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Siderophore‐mediated cell signalling in Pseudomonas aeruginosa: divergent pathways regulate virulence factor production and siderophore receptor synthesis

Cited by 191 publications

References 61 publications

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

A mutant in one of two exbD loci of a TonB system in Flavobacterium psychrophilum shows attenuated virulence and confers protection against cold water disease

Genetic and Transcriptional Analysis of the Siderophore Malleobactin Biosynthesis and Transport Genes in the Human Pathogen Burkholderia pseudomallei K96243

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