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Avian malaria in the Swallow
Krausová, Simona ; Munclinger, Pavel (advisor) ; Votýpka, Jan (referee)
Long-distance migratory birds can encounter a wide range of parasites. Various populations of birds within one species use different migration routes and can also winter in different places. It can be supposed that birds which use different migration routes should be infected with different parasites. To study the relationship between the migration and the distribution of parasites we chose the worldwide species barn swallow (Hirundo rustica) and the avian malaria parasites. Swallows migrate long distances in different migrating routes. Some populations of swallows do not migrate, they are resident. This is the reason why swallow is a good model species for finding the answers to questions whether the populations using different migration routes are infected with different parasites or not and whether or not the diversity of parasites is wider in populations which migrate long distances in comparison with the resident populations. The malaria lineages of the genus Plasmodium and Haemoproteus were detected using nested PCR and sequencing. 1242 samples from 8 different localities from the USA, Europe and Asia were tested. We detected 24 different malaria lineages. Within the genus Plasmodium 4 of 16 lines were detected for the first time and in the genus Haemoproteus 3 of 6 lines were detected for the first...
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Can avian malaria affect the reproductive success of the host?
Krausová, Simona ; Munclinger, Pavel (advisor) ; Vinkler, Michal (referee)
Malarial deseases caused by intracellular parasites of birds is very common. Even if infection doesn't lead to the death of infected individuals, they may suffer alternations of different levels of fitness, which may also consequently harm their reproductive success rates. Infected individuals, due to their poor physical condition, may lay lower quality eggs, breed less viable offspring, have reduced frequency of feeding their chicks, etc. While it may seem that malarial parasites undoubtedly negatively affect their hosts's reproduction, there are numerous studies which do no support such prediction. These differences in individual studies may be due to various testing methods used in the indicated studies. Because of various testing methods, there also may appear other possible problems which can more or less affect the detection rate of malaria parasites.
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Acyclic nucleoside bis-phosphonates as potent inhibitors of 6-oxopurine phosphoribosyltransferases
Špaček, Petr ; Keough, D. T. ; Vrbková, Silvie ; Slavětínská, Lenka ; Janeba, Zlatko ; Naesens, L. ; Edstein, M. D. ; Chavchich, M. ; Wang, T. H. ; de Jersey, J. ; Guddat, L. W. ; Hocková, Dana
Hypoxanthine-guanin-(xanthine) phosphoribosyltransferase (HG(X)PRT) is critical for the survival of malarial parasites Plasmodium falciparum and Plasmodium vivax. These parasites rely on HG(X)PRT to make 6-oxopurine nucleoside monophosphates. Specific acyclic nucleoside phosphonates (ANPs) inhibit HG(X)PRT and thus have an anti-plasmodial activity. Crystal structures of human HGPRT in complex with several ANP-based inhibitors suggested that attachment of the second phosphonate group which could occupy the pyrophosphate binding site may lead to increased affinity of these compounds.
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Acyclic nucleoside bisphosphonates as inhibitors of 6-oxopurine phosphoribosyltransferases: Potential antimalarial and antibacterial agents
Hocková, Dana ; Keough, D. T. ; Špaček, Petr ; Janeba, Zlatko ; Edstein, M. D. ; Chavchich, M. ; Wang, T. H. ; Eng, W. S. ; West, N. P. ; de Jersey, J. ; Guddat, L. W.
Acyclic nucleoside phosphonates (ANPs) that contain a 6-oxopurine base are good inhibitors of the human, Plasmodium falciparum, P. vivax, Escherichia coli and Mycobacterium tuberculosis 6-oxopurine phosphoribosyltransferases (PRTases), key enzymes of the purine salvage pathway. Chemical modifications based on the crystal structures of several inhibitors in complex with human HGPRTase have led to the design of new ANPs. These novel compounds contain a second phosphonate group attached to the ANP scaff old. The crystal structures of these inhibitors in complex with human HGPRTase show that they can fill three critical locations in the active site: the binding sites of the purine base, the 5’-phosphate group and pyrophosphate. Prodrugs have been synthesized and have been shown to arrest the growth of P. falciparum in erythrocyte culture. Prodrugs of selected ANPs also inhibit the growth of Mycobacterium tuberculosis in cell-based assays.
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Acyclic Nucleoside Phosphonates as Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: New Anti-Malarial Chemotherapy Leads
Hocková, Dana ; Holý, Antonín ; Česnek, Michal ; Baszczyňski, Ondřej ; Tichý, Tomáš ; Krečmerová, Marcela ; Janeba, Zlatko ; Skinner-Adams, T. S. ; Naesens, L. ; Keough, D. T. ; de Jersey, J. ; Guddat, L. W.
Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) is a widely recognized target for the discovery of new anti-malarial drugs. Specific acyclic nucleoside phosphonates (ANPs) inhibit HGXPRTase and possess anti-plasmodial activity. Within the framework of a SAR-study, the classical ANPs (e.g. PME-, PMP- and HPMP-derivatives) as well as novel series of compounds were tested to investigate their efficiency and selectivity on the inhibition of P. falciparum, P. vivax and human enzyme.
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