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The energy parasite hypothesis originally formulated by Moulder, 1962 was that chlamydial multiplication depends on ATP and other high energy compounds generated by the dissimulation of glucose by the host. Experimental evidence for this came from the discovery of an ATP-ADP exchange activity in C. psittaci [Hatch et al., 1982]. The presence of ATP / ADP translocase activity was therefore expected, and was confirmed when two genes encoding the transporter proteins, Npt1_Ct and Npt2_Ct were identified in the whole genomic sequence . These proteins were paralogues of ADP/ATP translocases of Rickettsia, mitochondria and chloroplasts [Tjaden et al., 1999]. The gene products were active were active as ATP transporters when they were expressed as recombinant proteins in Escherichia coli.  Similar genes are also present in C. pneumoniae. Npt1_Ct mediated ATP transport by receiving ATP in exchange for ADP. Npt2_Ct catalysed the net uptake of all four ribonucleoside triphosphates [Tjaden et al., 1999]. The presence and expression of genes involved in metabolic pathways for ATP generation [Hatch et al., 1982; ] suggests that chlamydiae are not strict requirers [auxotrophs] for ATP. However, the functional activity of Npt1_Ct [4] indicates that chlamydiae acquire at least a portion of their ATP from the host cell. Interestingly, studies of DNA vaccines in mice indicate that these gene products might be potential candidates for generating protective immunity (see: vaccine development).

It had long been thought that, as a consequence of intracellular parasitism which offered a rich supply of high energy compounds from the host, chlamydiae had lost any significant capability of generating there own high energy compounds [Moulder, 1974]. One of the surprises of genomic sequencing, therefore, was the finding that chlamydiae themselves have energy-generating metabolic capabilities beyond those of many free-living organisms [Stephens et al., 1998].  Nevertheless, of all genomes completely sequenced to date, C. trachomatis serovar D so far contain the smallest repertoire of genes encoding enzymes of nucleotide metabolism, with no homologues of genes in the nucleotide synthesis or nucleobase pathways [Tjaden et al., 1999; Stephens et al., 1998]. In contrast, both C. pneumoniae and C. muridarum (mouse pneumonitis agent) unexpectedly contain some genes for uracil / uridine salvage and ATP to GTP conversion [Stephens et al., 1998]. Analysis of C. trachomatis gene transcription in active versus persistent infection suggests that, in the first phase of active infection, ADP/ATP exchange provides the energy required for metabolism with glycolysis supplementing host-derived ATP. In persistent infection [human monocytes, synovium, Hep2 cells] host not chlamydial-produced ATP is the primary energy source. The metabolic rate in persistent C. trachomatis infection is lower than in actively growing cells, as judged from chlamydial rRNA transcript levels [Gerard et al., 2002; see also: persistent infection; also:  ATP/ADP translocases in chlamydial evolution]. 

Web resources

Energy related proteins translated by C. pneumoniae VR 1310 purified EB are given in table 3 of the chlamydial proteomics database , Aarhus, Denmark [see also: VanDahl et al., 2001].  The Biochemical Pathways Feature of the Los Alamos STD organisms sequence database gives good graphics of chlamydial bio-energetic pathways.

[MEW] Updated May 2002

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References

Gerard, H. C., Freise, J., Wang, Z. et al., (2002) Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection. Microbes and Infection 4, 13 - 22.

Hatch, T. P., Al-Hossainy, E. & Silverman, J. A. (1982). Adenine nucleotide and lysine transport in Chlamydia psittaci. Journal of Bacteriology 150, 662-667.

McClarty, G. (1999). Chlamydial metabolism as inferred from the complete genome sequence. In Chlamydia: Intracellular Biology, Pathogenesis, and Immunity, pp. 69-100. Edited by R. S. Stephens. Washington, D.C.: ASM Press. ISBN 1-55581-155-8.

Moulder, J. W. (1962). The biochemistry of intracellular parasitism. University of Chicago Press, Illinois, USA. [Classic text at the time].

Moulder, J. W. (1974). Intracellular parasitism. Life in an extreme environment. Journal of Infectious Diseases 130, 300 - 306.

Stephens, R. S., Kalman, S., Lammel, C. et al., (1998). Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754 - 759. +

Tjaden, J., Winkler, H. H., Schwoppe, C., Van Der Laan, M., Mohlmann, T.  Neuhaus, H. E. (1999).  Two nucleotide transport proteins in Chlamydia trachomatis, one for net nucleoside triphosphate uptake and the other for transport of energy. Journal of Bacteriology 181, 1196 - 1202. Full article

van Dahl, B. B., Birkelund, S. , Demol, H., Hoorelbeke, B., Christiansen, G., Vandekerckhove, J. & Gevaert K. (2001). Proteome analysis of the Chlamydia pneumoniae elementary body. Electrophoresis 22, 1204 - 1223.

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