Phenazine Pigments in Pseudomonas aeruginosa Infection

Sorensen, Ricardo U.; Joseph, Fred

doi:10.1007/978-1-4615-3036-7_3

Cited by 12 publications

(8 citation statements)

References 42 publications

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“…The results were interpreted in terms of a model in which phenazines are one component of a multifactorial killing process. Phenazines are toxic to a variety of cell types and are thought to act by generating reactive oxygen species by redox cycling (59). For strain PAO1, we found no convincing indication that pyocyanin or any other phenazine plays a direct role in killing C. elegans.…”

Section: Vol 183 2001contrasting

confidence: 62%

Pseudomonas aeruginosa PAO1 Kills Caenorhabditis elegans by Cyanide Poisoning

2001

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In this report we describe experiments to investigate a simple virulence model in which Pseudomonas aeruginosa PAO1 rapidly paralyzes and kills the nematode Caenorhabditis elegans. Our results imply that hydrogen cyanide is the sole or primary toxic factor produced by P. aeruginosa that is responsible for killing of the nematode. Four lines of evidence support this conclusion. First, a transposon insertion mutation in a gene encoding a subunit of hydrogen cyanide synthase (hcnC) eliminated nematode killing. Second, the 17 avirulent mutants examined all exhibited reduced cyanide synthesis, and the residual production levels correlated with killing efficiency. Third, exposure to exogenous cyanide alone at levels comparable to the level produced by PAO1 killed nematodes with kinetics similar to those observed with bacteria. The killing was not enhanced if hcnC mutant bacteria were present during cyanide exposure. And fourth, a nematode mutant (egl-9) resistant to P. aeruginosa was also resistant to killing by exogenous cyanide in the absence of bacteria. A model for nematode killing based on inhibition of mitochondrial cytochrome oxidase is presented. The action of cyanide helps account for the unusually broad host range of virulence of P. aeruginosa and may contribute to the pathogenesis in opportunistic human infections due to the bacterium.Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium that is virulent towards a wide range of organisms, including bacteria, plants, nematodes, insects, and mammals (5,9,17,19,35,36,41,48,49,62). In humans, P. aeruginosa chronically infects the lungs of most cystic fibrosis patients, causes serious infections of burn wounds and eye lesions, and causes systemic infections of immunocompromised individuals (21,29,33,39). The bacterium's pathogenic versatility is reflected in its large arsenal of secreted and surface-associated virulence factors and in the complexity of the regulatory circuitry with which it controls these factors. Among the specific virulence factors that it produces are adhesins, such as pili and filamentous hemagglutinin (14, 39); protein toxins, such as phospholipase, proteases, and ADP-ribosylating enzymes (39, 64); and small-molecule poisons, such as phenazines, rhamnolipid biosurfactant, and cyanide (4,8,44). Additionally, the genome of P. aeruginosa boasts the highest proportion of predicted regulatory genes of any of the bacterial genomes sequenced to date (61), which is indicative of the bacterium's remarkable ability to adapt and thrive in numerous pathogenic and nonpathogenic environments.Several model systems for Pseudomonas pathogenesis have been developed recently, and numerous genes required for virulence towards model hosts are also required for virulence towards mammals. For example, mutants of P. aeruginosa PA-14 exhibiting reduced virulence towards Arabidopsis or Caenorhabditis elegans also exhibit reduced virulence in a burned-mouse infection model (49,50,62). In addition, a putative Pseudomonas signal transduction gene cluster requi...

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Section: Vol 183 2001contrasting

confidence: 62%

Pseudomonas aeruginosa PAO1 Kills Caenorhabditis elegans by Cyanide Poisoning

2001

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“…Despite intensive in vitro analyses of phenazines, the physiological significance of their role in P. aeruginosa pathogenesis in mammals has been controversial (61). Before our studies, there had been no demonstration of their role in vivo.…”

Section: What Types Of Virulence Mechanisms Are Conserved Through Evomentioning

confidence: 94%

Plants and animals share functionally common bacterial virulence factors

Rahme

Ausubel

Cao

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

365

306

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By exploiting the ability of Pseudomonas aeruginosa to infect a variety of vertebrate and nonvertebrate hosts, we have developed model systems that use plants and nematodes as adjuncts to mammalian models to help elucidate the molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable degree of conservation in the virulence mechanisms used by P. aeruginosa to infect hosts of divergent evolutionary origins.

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“…Besides the already-mentioned chlororaphine ( 2 , a 1:1 complex of phenazine-1-carboxamide and its 5,10-dihydro derivative; Figure ) 15,16 and iodinin ( 6 , 1,6-dihydroxyphenazine-5,10-dioxide; Figure ), other phenazines produced by pseudomonads include aeruginosins A ( 4 ) and B ( 5 ), isolated from P. aeruginosa and P. iodina , and the dimeric structure ( 7 ), di(2-hydroxy-1-phenazinyl)methane, isolated from a pigmentation mutant of P. aureofaciens (Figure ). − ,− …”

Section: 1 Pseudomonadsmentioning

confidence: 99%