Iron-sulfur flavoproteins (Isf) are flavin mononucleotide (FMN)- and FeS cluster-containing proteins commonly encountered in anaerobic prokaryotes. However, with the exception of Isf from Methanosarcina thermophila, which participates in oxidative stress management by removing oxygen and hydrogen peroxide, none of these proteins has been characterized in terms of function. Trichomonas vaginalis, a sexually transmitted eukaryotic parasite of humans, was found to express several iron-sulfur flavoprotein (TvIsf) homologs in its hydrogenosomes. We show here that in addition to having oxygen-reducing activity, the recombinant TvIsf also functions as a detoxifying reductase of metronidazole and chloramphenicol, both of which are antibiotics effective against a variety of anaerobic microbes. TvIsf can utilize both NADH and reduced ferredoxin as electron donors. Given the prevalence of Isf in anaerobic prokaryotes, we propose that these proteins are central to a novel defense mechanism against xenobiotics.

• MeSH
• antitrichomonádové látky farmakologie   MeSH
• ferredoxiny metabolismus   MeSH
• flavoproteiny metabolismus   MeSH
• geny hub MeSH
• katalýza MeSH
• léková rezistence MeSH
• metronidazol chemie   farmakologie   MeSH
• molekulární sekvence - údaje MeSH
• NAD metabolismus   MeSH
• proteiny obsahující železo a síru metabolismus   MeSH
• sekvence aminokyselin MeSH
• subcelulární frakce účinky léků   metabolismus   MeSH
• Trichomonas vaginalis metabolismus   MeSH
• vodík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitrichomonádové látky MeSH
• ferredoxiny MeSH
• flavoproteiny MeSH
• metronidazol MeSH
• NAD MeSH
• proteiny obsahující železo a síru MeSH
• vodík MeSH

Iron plays a crucial role in metabolism as a key component of catalytic and redox cofactors, such as heme or iron-sulfur clusters in enzymes and electron-transporting or regulatory proteins. Limitation of iron availability by the host is also one of the mechanisms involved in immunity. Pathogens must regulate their protein expression according to the iron concentration in their environment and optimize their metabolic pathways in cases of limitation through the availability of respective cofactors. Trichomonas vaginalis, a sexually transmitted pathogen of humans, requires high iron levels for optimal growth. It is an anaerobe that possesses hydrogenosomes, mitochondrion-related organelles that harbor pathways of energy metabolism and iron-sulfur cluster assembly. We analyzed the proteomes of hydrogenosomes obtained from cells cultivated under iron-rich and iron-deficient conditions employing two-dimensional peptide separation combining IEF and nano-HPLC with quantitative MALDI-MS/MS. We identified 179 proteins, of which 58 were differentially expressed. Iron deficiency led to the upregulation of proteins involved in iron-sulfur cluster assembly and the downregulation of enzymes involved in carbohydrate metabolism. Interestingly, iron affected the expression of only some of multiple protein paralogues, whereas the expression of others was iron independent. This finding indicates a stringent regulation of differentially expressed multiple gene copies in response to changes in the availability of exogenous iron.

• MeSH
• energetický metabolismus MeSH
• hmotnostní spektrometrie MeSH
• lidé MeSH
• organely metabolismus   ultrastruktura   MeSH
• oxidace-redukce MeSH
• proteom metabolismus   MeSH
• proteomika MeSH
• protozoální proteiny chemie   metabolismus   MeSH
• regulace genové exprese MeSH
• shluková analýza MeSH
• síra metabolismus   MeSH
• Trichomonas vaginalis genetika   metabolismus   MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteom MeSH
• protozoální proteiny MeSH
• síra MeSH
• železo MeSH