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Mycoplasma pyrimidine deoxynucleotide biosynthesis

molecular characterization of a new family flavin-dependent thymidylate synthase

Wehelie, Rahma (2006). Mycoplasma pyrimidine deoxynucleotide biosynthesis. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2006:76
ISBN 91-576-7125-7
[Doctoral thesis]

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Mycoplasmas (class mollicutes) are the smallest self-replicating bacteria. They are obligate parasites in a wide range of organisms, including humans, plants, and animals. This thesis describes studies related to Mycoplasma mycoides subsp. mycoides Small Colony (MmmSC), the etiological agent of contagious bovine pleuropneumoniae, Mycoplasma capricolum (Mcap), causing caprine pneumonia, Mycoplasma hyopneumoniae (Mhp), the etiological agent of porcine enzootic pneumonia, Ureaplasma urealyticum (Uu), a commensal of human urogenital tract causing nongonococcal urethritis, Mycoplasma genitalium (Mg), a causative agent of nongonococcal, chlamydia-negative urethritis, and Mycoplasma pneumoniae (Mpn) causing atypical pneumonia and tracheobronchitis. The first part concerns deoxynucleoside metabolism in Uu and growth inhibition of Uu and Mpn by nucleoside analogs. The uptake and metabolism of the deoxynucleosides, thymidine (dThd), deoxyuridine, deoxycytidine were studied and all these deoxynucleosides were readily taken up by Uu and dThd showed the highest rate of uptake. Pyrimidine nucleosides e.g., fluoropyrimidines gave complete inhibition of Uu growth. The addition of dUrd and dThd to the growth medium abolished inhibitory effect. These results suggested a new pathway of thymidylate synthesis in Uu. The second part deals with identification of a new family of flavin-dependent thymidylate synthases (FDTS) in mycoplasmas. Thymidylate synthases (TS) are essential enzymes in the de novo synthesis of thymidylate and are coded either by thyA or thyX genes. Analysis of the fully sequenced Mycoplasma genomes revealed that there were no TS genes annotated in the genomes of Uu, MmmSC, Mhp, and Mcap. Still, TS activities were detected in Uu and MmmSC extracts. By using a bioinformatics approach together with biochemical methods putative genes for (FDTS) were identified in Uu, MmmSC, Mhp and Mcap genomes and functional verified. New members of this family were also discovered in Mg and Mpn, which also have the thyA genes. These mycoplasma FDTS have similar catalytic activity to the ThyX proteins, but share very little sequence homology to the known bacterial ThyX. The sequence homologies within Mycoplasma FDTS were also very low. Since Mycoplasma FDTS share no sequence or structural homology to ThyA or ThyX this makes them promising targets for future design of new antibiotics.

Authors/Creators:Wehelie, Rahma
Title:Mycoplasma pyrimidine deoxynucleotide biosynthesis
Subtitle:molecular characterization of a new family flavin-dependent thymidylate synthase
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :September 2006
Number of Pages:35
ALLI. Carnrot, C.*, Wehelie, R.*, Eriksson, S., Bölske, G., and Wang, L. (2003) Molecular characterization of thymidine kinase from Ureaplasma urealyticum: nucleoside analogues as potent inhibitors of mycoplasma growth. Mol Microbiol. 50, 771-780. (*These authors contribute equally). II. Rahma Wehelie, Staffan Eriksson and Liya Wang (2004). Effect of Fluoropyrimidines on the Growth of Ureaplasma urealyticum. Nucleosides, Nucleotides & Nucleic Acids. 2,1499-1502. III.Rahma Wehelie, Staffan Eriksson, Göte Swedberg, Göran Bölske and Liya Wang (2006). Thymidylate synthases of Mycoplasma mycoides subsp. mycoides SC and Ureaplasma urealyticum are flavin-dependent (manuscript). IV.Rahma Wehelie, Staffan Eriksson, Göte Swedberg, Göran Bölske and Liya Wang (2006). A new family of flavin-dependent thymidylate in pathogenic mycoplasmas. (manuscript).
Place of Publication:Uppsala
ISBN for printed version:91-576-7125-7
Publication Type:Doctoral thesis
Full Text Status:Public
Agrovoc terms:mycoplasma, ureaplasma, nucleosides, growth, inhibition, enzymes, metabolism
Keywords:mycoplasmas, ureaplasma, thymidylate synthase, flavin-dependent thymidylate synthase, nucleoside analogs, nucleoside metabolism
Permanent URL:
ID Code:1194
Department:(VH) > Dept. of Molecular Biosciences (until 070101)
Deposited By: Rahma Wehelie
Deposited On:13 Sep 2006 00:00
Metadata Last Modified:02 Dec 2014 10:10

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