<i>Bordetella pertussis</i>
            Autoregulates Pertussis Toxin Production through the Metabolism of Cysteine

Bogdan, John A.; Nazario-Larrieu, Javier; Sarwar, Jawad; Alexander, Peter; Blake, M. S.

doi:10.1128/iai.69.11.6823-6830.2001

Cited by 36 publications

(33 citation statements)

References 56 publications

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“…In Mycobacterium tuberculosis, the cysDNC operon involved in the sulfate activation pathway forms a stress-induced operon (60), while many thiol and cysteine metabolism genes are part of the sigH regulon necessary for optimal survival of the bacterium in macrophages (52). Cysteine metabolism is also involved in the regulation of toxin in Bordetella pertussis (4), and autoinducer 2, a signaling molecule derivative of the sulfur metabolism conserved in both gram-positive and gram-negative bacteria, is involved in interspecies communication and regulation of virulence factors (54,68). Lastly, methionine is one of the key amino acids limiting the growth of Lactococcus lactis in dairy fermentations.…”

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Sulfur Amino Acid Metabolism and Its Control in Lactococcus lactis IL1403

et al. 2005

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Cysteine and methionine availability influences many processes in the cell. In bacteria, transcription of the specific genes involved in the synthesis of these two amino acids is usually regulated by different mechanisms or regulators. Pathways for the synthesis of cysteine and methionine and their interconversion were experimentally determined for Lactococcus lactis, a lactic acid bacterium commonly found in food. A new gene, yhcE, was shown to be involved in methionine recycling to cysteine. Surprisingly, 18 genes, representing almost all genes of these pathways, are under the control of a LysR-type activator, FhuR, also named CmbR. DNA microarray experiments showed that FhuR targets are restricted to this set of 18 genes clustered in seven transcriptional units, while cysteine starvation modifies the transcription level of several other genes potentially involved in oxidoreduction processes. Purified FhuR binds a 13-bp box centered 46 to 53 bp upstream of the transcriptional starts from the seven regulated promoters, while a second box with the same consensus is present upstream of the first binding box, separated by 8 to 10 bp. O-Acetyl serine increases FhuR binding affinity to its binding boxes. The overall view of sulfur amino acid metabolism and its regulation in L. lactis indicates that CysE could be a master enzyme controlling the activity of FhuR by providing its effector, while other controls at the enzymatic level appear to be necessary to compensate the absence of differential regulation of the genes involved in the interconversion of methionine and cysteine and other biosynthesis genes.Sulfur is a constituent of many indispensable components of the cell, such as cysteine, methionine, thiamine, biotin, lipoic acid, coenzyme A, etc. Among these compounds, cysteine has a central role, since its de novo synthesis represents the main pathway of sulfur acquisition in microorganisms and plants. Cysteine is thus the principal metabolite from which most sulfur-containing compounds are built. It is also an essential amino acid of the catalytic domain of universal proteins having iron-sulfur clusters, such as cytochromes and aconitase. Cysteine also plays a central role in protein folding, assembly, and stability via the formation of disulfide bounds. Moreover, cysteine-derived proteins, such as thioredoxin and glutathione, play a central role in the protection against oxidative stress. The second sulfur amino acid, methionine, is a key compound controlling the initiation of translation and is crucial to a variety of methyltransferase reactions.As a result of the essential roles in metabolism, cysteine and methionine supply might be limiting for bacterial growth in different situations of importance for humans, such as pathogenic events or fermentation processes. For example, methionine availability is limiting for growth of group B streptococci in plasma (65). Sulfur amino acid biosynthesis genes have been characterized as virulence factors in Brucella melitensis (48), Haemophilus parasuis (36), and Salmonel...

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Sulfur Amino Acid Metabolism and Its Control in Lactococcus lactis IL1403

et al. 2005

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“…Porém, com concentrações de 300 mM, a pureza radioquímica foi inferior aos 90%. Em teoria, este estudo indicou que o complexo radiomarcado não apresentaria transquelação in vivo, uma vez que a concentração de cisteína no organismo é muito baixa, sendo que no plasma humano ela varia entre 0,03 e 0,108 mM (Bogdan et al, 2001;Medical, 2006). Quando a análise dos dados é feita em relação ao tempo de incubação de 4 h, pôde-se constatar um pequeno decréscimo na estabilidade se comparado com os resultados de uma hora.…”

Section: Discussionunclassified

Estudos in vitro e in vivo de análogo da timidina marcada com complexo organometálico de tecnécio-99m para potencial uso em diagnóstico tumoral

Santos¹,

Faintuch²,

Teodoro³

2008

Rev. Bras. Cienc. Farm.

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“…Sulfate has been shown to modulate, or down-regulate, transcription of the Bvg-regulated genes, including pertussis toxin (19) and, recently, bacterial conversion of cysteine to sulfate has been reported to promote modulation (2). Assembled pertussis toxin accumulates in the periplasm prior to secretion.…”

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“…Under nonpermissive conditions, such as in the presence of high levels of sulfate ions, transcription of the B. pertussis virulence factors, including pertussis toxin, is repressed (19). Recently, it has been demonstrated that cysteine in the culture medium can serve as a precursor for sulfate production, which then modulates expression of the Bvg-regulated genes (2). Cysteine has been reported to be an essential amino acid for growth of B. pertussis, an observation that is supported by the presence of defective copies of the genes for cysteine biosynthesis in the preliminary genome sequence of B. pertussis that are intact in the preliminary genome of Bordetella bronchiseptica.…”

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Reduced Glutathione Is Required for Pertussis Toxin Secretion by Bordetella pertussis

2003

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The abilities of cysteine-containing compounds to support growth of Bordetella pertussis and influence pertussis toxin transcription, assembly, and secretion were examined. Cysteine is an essential amino acid for B. pertussis and must be present for protein synthesis and bacterial growth. However, cysteine can be metabolized to sulfate, and high concentrations of sulfate can selectively inhibit transcription of the virulence factors, including pertussis toxin, via the BvgAS two-component regulatory system in a process called modulation. In addition, pertussis toxin possesses several disulfide bonds, and the cysteine-containing compound glutathione can influence oxidation-reduction reactions and perhaps disulfide bond formation. Bacterial growth was not observed in the absence of a source of cysteine. Oxidized glutathione, as a sole source of cysteine, also did not support bacterial growth. Cysteine, cystine, and reduced glutathione did support bacterial growth, and none of these compounds caused modulation at the concentrations tested. Similar amounts of periplasmic pertussis toxin were detected regardless of the source of cysteine; however, in the absence of reduced glutathione, pertussis toxin was not efficiently secreted. Addition of the reducing agent dithiothreitol was unable to compensate for the lack of reduced glutathione and did not promote secretion of pertussis toxin. These results suggest that reduced glutathione does not affect the accumulation of assembled active pertussis toxin in the periplasm but plays a role in efficient pertussis toxin secretion by the bacterium.

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Bordetella pertussis Autoregulates Pertussis Toxin Production through the Metabolism of Cysteine

Abstract: 2؊ . Therefore, the combined presence and metabolism of cysteine may be an important mechanism in the pathogenesis of B. pertussis.

Cited by 36 publications

References 56 publications

Sulfur Amino Acid Metabolism and Its Control in Lactococcus lactis IL1403

Sulfur Amino Acid Metabolism and Its Control in Lactococcus lactis IL1403

Estudos in vitro e in vivo de análogo da timidina marcada com complexo organometálico de tecnécio-99m para potencial uso em diagnóstico tumoral

Reduced Glutathione Is Required for Pertussis Toxin Secretion by Bordetella pertussis

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