6+7+The+Apicomplexa+Malaria

6+7+The+Apicomplexa+Malaria - TheApicomplexans...

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The Apicomplexans Plasmodium  spp . Babesia  spp . Toxoplasma gondii Isospora belli Cryptosporidium parvum Cyclospora cayetanensis *
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All apicomplexans are  obligate intracellular parasites . This  means that they only grow and replicate inside host cells. Subsets of this diverse group  •coccidia ( Toxoplasma, Cryptospridium, Cyclospora, Isospora ) •piroplasms ( Babesia ) •malarias ( Plasmodium ) •gregarines (no human parasites) •haemogregarines (no human parasites) The Apicomplexa
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complex life cycle:  sporozoites  infect host  ingested in oocysts   ( Toxoplasma,   Isospora, Cryptosporidium, Cyclospora) injected by an insect vector   ( Plasmodium, Babesia )  host cells lyse, releasing  parasite to infect new cells   repeated replication differentiation to gamonts    gametes  (1N)   zygote  (2N) meiosis to create sporozoites (1N) The Apicomplexa
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characterized by:   •the apical complex : unique organelles at parasite apex used for host cell invasion micronemes rhoptries secrete proteins to establish a vacuole conoid : (some species) mechanical aid to invasion •the apicoplast : degenerate chloroplast (plastid) essential function The Apicomplexa
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•Chloroplasts organisms that capture light energy during photosynthesis. They are  believed to have originated from  cyanobacteria  through  endosymbiosis.  Chloroplasts have their own genome, which is reduced  but similar to that of cyanobacteria. The apicoplast is a non-photosynthetic plastid . •evolved via secondary endosymbiosis ancestral genome >150 kb   circular 35 kb genome  lost ability to photosynthesize >500 nuclearly encoded proteins are imported to plastid •essential organelle   inhibited by macrolide antibiotics plant-like = drug target since we are not biochemically “like” plants The Apicoplast
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Apicoplast Function several prokaryotic biochemical pathways have been localized  in this organelle  – isoprenoid precursors – fatty acids – heme – Fe-S clusters – lipoic acid antibiotics that inhibit expression of apicoplast genes cause a  ‘‘delayed death’’   antibiotics kill the progeny of treated  eventually stops)… – The antibiotics can be removed and the parasites still die later on – A delayed death suggests that something essential for parasite replication  is used up over time What is the essential target? Inhibiting this ought to kill parasites and be  a great way to develop new drugs.
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6+7+The+Apicomplexa+Malaria - TheApicomplexans...

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