Partner und Internationale Organisationen
(Englisch)
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BE, BG, CH, DE, ES, FR, GR, HR, HU, IE, IT, MK, PL, SE, UK
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Abstract
(Englisch)
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Chlamydia are an obligate intracellular pathogens in humans and animals. Acute exposure during pregnancy to Chlamydophila abortus, for example, can lead to abortion, posing not only a substantial zoonotic risk for humans, but also causing significant reproductive losses to herds. Identification of 'problem' animals in herds, as part of the strategy to follow and control disease progression, is currently dependent on assays designed to identify the agent of acute infection, the infectious particle or elementary body (EB). Chlamydia can also enter a chronic or 'persistent' state which involves interruption to the cell cycle. The resultant aberrant body (AB), sequested within host cells, is currently difficult if not impossible to detect in vivo. This reservoir of persistent forms presents a potential source of infection which can be stimulated to re-enter the developmental cycle, releasing the infectious EB and initiating a new round of acute infection. A major problem in risk management is how to go about identifying chronic infections. We hypothesized that the clue to an effective test is to establish the nature of the chlamydial antigenic profile of chronically infected animals. We have been attempting to establish the nature of this profile by identification and expression of persistence (chronic infection) regulated chlamydial genes and proteins. Our in vitro models of persistence center around analysing proteins we have identified as potential regulators of the developmental cycle. This work has been successful and we have generated evidence to support roles for differentially regulated chlamydial GTPases HflX and yhbZ in the chlamydial cell cycle via expression studies in E. coli. We have raised a number of specific monoclonal and polyclonal antibodies against both these proteins and are using these to characterise expression during normal development and persistent chlamydial infections in vitro. These results support our hypothesis that proteins specifically up or down regulated in persistence (see Polkinghorne et al., 2006) are likely to be key regulators of the developmental cycle and hence optimal targets for screening persistence in farm animals. This work has now been submitted for publication (Chlamydia HflX is a novel evolutionarily conserved GTPase which associates with the 50S large ribosomal subunit (2008) Polkinghorne A., Ziegler U., González-Hernández Y., Pospischil A., Timms P., Vaughan L). A companion manuscript on the GTPase yhbZ (Chlamydophila abortus YhbZ associates with the bacterial large ribosomal subunit. Polkinghorne A, Brugnera E, Summersgill J, Pospischil A, Timms P, Vaughan L) has also been submitted. Mechanisms and routes of infection are important considerations when considering how infections persist in animal populations. To this end, we could show that amphibians could be an important reservoir of chlamydia in farmland (Blumer C, Zimmermann DR, Weilenmann R, Vaughan L, Pospischil A. (2007) Chlamydiae in free-ranging and captive frogs in Switzerland. Vet Pathol. 44, 144-50) and that intensively kept animals have higher levels of infection (Becker A, Lutz-Wohlgroth L, Brugnera E, Lu ZH, Zimmermann DR, Grimm F, Grosse Beilage E, Kaps S, Spiess B, Pospischil A, Vaughan L. (2007) Intensively kept pigs pre-disposed to chlamydial associated conjunctivitis. J Vet Med A Physiol Pathol Clin Med. 54, 307-13). Eye infections could be an as yet underestimated source of infection within herds (Polkinghorne A., Borel N., Becker A., Lu Z.H., Zimmermann D.R., Brugnera E., Pospischil A. and Vaughan L. (2008) Molecular evidence for chlamydial infections in the eyes of sheep Veterinary Microbiology, in press). In previous studies, the question was raised as to whether Amoeba could act as vectors for transmission of chlamydia, as they have been shown to do this for the chlamydia-like organisms. We could show unequivocally that this was not the case for Cp. abortus, and by so doing defined an important difference in the biology between the chlamydia and the chlamydia-like which opens avenues for further research and possibly for treatment (Wirz M., Polkinghorne A., Dumrese C., Ziegler U., Greub G., Pospischil A., Vaughan L. (2008) Predator or prey? Chlamydophila abortus infections of a free-living amoebae, Acanthamoeba castellani 9GU Microbes and Infection. 10, 591-597).
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