A Nutrition-Inhibition Hypothesis of Pathogenicity

Garber, E. D.

doi:10.1086/281925

Cited by 90 publications

(27 citation statements)

References 6 publications

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“…In keeping with Garber's nutrition-inhibition model [10], it is tempting to speculate that the heaviest biosynthetic demands on P. aeruginosa are associated with initiating a lung infection, and with the associated growth to very high cell densities in CF sputum. The decrease in fitness that we observed (W = 0.89) corresponds to a twofold reduction in cell numbers (compared to the competitor, lacZ-marked PAO1) over the course of 24 h growth in SCFM.…”

Section: Discussionmentioning

confidence: 91%

“…In 1956, Edward Garber proposed a ''nutrition-inhibition hypothesis'' of pathogenicity, in which he reasoned that infection not only required a pathogen to avoid the host's defence mechanisms, but also required that it could utilize the host environment as a growth medium [10]. The implication is that virulence can be diminished by interfering with the biosynthetic requirements of a bacterium at its site of infection [5,11].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the indole-3-glycerol phosphate synthase from Pseudomonas aeruginosa PAO1

2012

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Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic infections in the lungs of individuals with cystic fibrosis. It is intrinsically resistant to many antibiotics, and resistance is emerging rapidly to those drugs that currently remain efficacious. Therefore, there is a pressing need to identify new anti-pseudomonal drug targets. To this end, we have characterized the P. aeruginosa indole-3-glycerol phosphate synthase (PaIGPS). PaIGPS catalyzes the fifth reaction in the synthesis of tryptophan from chorismate--a reaction that is absent in mammals. PaIGPS was expressed heterologously in Escherichia coli, and purified with high yields. The purified enzyme is active over a broad pH range and has the highest turnover number of any characterized IGPS (k (cat) = 11.1 ± 0.1 s(-1)). These properties are likely to make PaIGPS useful in coupled assays for other enzymes in tryptophan biosynthesis. We have also shown that deleting the gene for PaIGPS reduces the fitness of P. aeruginosa strain PAO1 in synthetic cystic fibrosis sputum (relative fitness, W = 0.89 ± 0.02, P = 0.001). This suggests that de novo tryptophan biosynthesis may play a role in the establishment and maintenance of P. aeruginosa infections, and therefore that PaIGPS is a potential target for the development of new anti-pseudomonal drugs.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Characterization of the indole-3-glycerol phosphate synthase from Pseudomonas aeruginosa PAO1

2012

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“…methionine, might stimulate growth at one concentration but be strongly inhibitory at another. Even though the majority of metabolites were only tested at three levels of concentration, it may be inferred from the results reported above that inhibition-nutrition phenomena, as suggested by Garber (1956), play no part in the sporulation processes of P. tabacina.…”

Section: Discussionmentioning

confidence: 95%

Effects of Metabolites and Antlmetabolites on the Sporulation of Peronospora Tabaoina Adam. On Tobacco Leaf Disks

Shepherd¹,

Mandryk²

1964

Aust. Jnl. Of Bio. Sci.

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Summary.The effects of 148 metabolites and a~tinietabolites on the sporulation or"Peronospora tabacina Adam. on leaf disks of Nieotiand tubacum cv. Virginia Gold.have been determined.(1) Normal metabolites, with the exception of flavin adenine dinucleotide, had slight althoU:gh statistically significant effects on sporulation intensIty, which suggests that inhibition-nutri tion phenomena play no part in the sporulation process of P. tabacina.(2) Seven uracil analogues had an inhibitory effect on sporulation, and the reversal of inhibition by uracil suggests the active involvement of this compound in the sporulation process.(3) Canavanine at a final concentrat.ion of 120 ftgjml showed complete inhibition of sporulation. The reversal of the canavanine inhibition of sporulation by arginine, citrulline, and ornithine suggests the involvement of arginine and the functioning of an ornithine cycle in the sporulating system.(4) White, instead of the normal blue, conidia were produced in the presence of a number of sUlphur-contain ing compounds. It is suggested that this phenomenon depends on the chelating properties of these compounds towards copper ions, with the subsequent inactivation of tyrosinase activity in the conidia.(5) Sporulation intensities of 68 X 10'-}53 X 10 4 conidia per sqnare centimetre of leaf area were observed during the present study.

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“…The apparent dependence of a microbe on a potential host for most, if not all, of its nutritional needs and the restrictions that this dependency places on the hostparasite interaction has been recognized and debated for some time (Garber, 1956;Lewis, 1953). More recently, reports of the nutritional regulation of fungal genes thought to play a role in pathogenesis have refocused attention on these considerations (Straney and VanEtten, 1994;Talbot et al, 1993;Van den Ackerveken et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Cloning and Characterization of a General Amino Acid Control Transcriptional Activator from the Chestnut Blight FungusCryphonectria parasitica

Wang

Larson

Chen

et al. 1998

Fungal Genetics and Biology

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A Nutrition-Inhibition Hypothesis of Pathogenicity

Cited by 90 publications

References 6 publications

Characterization of the indole-3-glycerol phosphate synthase from Pseudomonas aeruginosa PAO1

Characterization of the indole-3-glycerol phosphate synthase from Pseudomonas aeruginosa PAO1

Effects of Metabolites and Antlmetabolites on the Sporulation of Peronospora Tabaoina Adam. On Tobacco Leaf Disks

Cloning and Characterization of a General Amino Acid Control Transcriptional Activator from the Chestnut Blight FungusCryphonectria parasitica

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