Iron from haemoglobin and haemin modulates nucleotide hydrolysis inTrichomonas vaginalis

Abstract

Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5’-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5’-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Trichomoniasis immunity and the involvement of the purinergic signaling

“…Iron from hemoglobin and hemin significantly increased NTP-Dase activity in fresh clinical T. vaginalis isolates from female patients and conversely, reduced the enzyme activity in isolates from male patients. Collectively, these results show the influence of iron in trichomonads ectonucleotidases through ATP degradation and adenosine production [118] . The ADA profile in different T. vaginalis isolates treated with different iron sources or with limited iron availability was also evaluated.…”

“…Besides serum restriction, the influence of iron on extracellular nucleotide hydrolysis in T. vaginalis isolates from female and male patients was evaluated [118] . Iron from hemoglobin and hemin significantly increased NTP-Dase activity in fresh clinical T. vaginalis isolates from female patients and conversely, reduced the enzyme activity in isolates from male patients.…”

Bulky Trichomonad Genomes: Encoding a Swiss Army Knife

“…In these environments, they scavenge nutrients from their hosts, which has enabled streamlining of their metabolism through the loss of certain metabolic enzyme genes [17][18][19]. For example, T. vaginalis cannot perform de novo nucleotide synthesis and must scavenge free nucleotides from its host [20]. Genes were also lost during the evolution of trichomonad hydrogenosomes; distant relatives of mitochondria that carry out an anaerobic form of respiration [21].…”

“…T. vaginalis secretes large quantities of cysteine protease into the growth medium when cultured in vitro, and T. vaginalis cysteine proteases are detectable in vivo, in vaginal washouts from infected patients [81,82]. T. vaginalis cysteine proteases also localise to cytoplasmic vesicles, lysosomes and surface membranes [81], and some are markedly upregulated in iron-enriched media; iron being a valuable cofactor for growth and replication of pathogenic protozoa [20,83]. Tri.…”

Prevalência de Trichomonas vaginalis em mulheres na idade fértil atendidas em equipe de saúde da família do Distrito Federal

“…A ausência de mitocôndrias é acompanhada de uma necessidade de ferro maior que a de outros protistas (Weinberg 1974;Schneider et al 2011;Beltrán et al 2013). Assim como outros microrganismos, o T. vaginalis depende do ferro para uma série de ações em seu metabolismo (Gorrell 1985;De Jesus et al 2006;Kühn 2009;Vieira et al 2015), inclusive ao regular a expressão gênica de algumas proteínas de superfície (Lehker et al 1991;Lehker & Alderete 1992;Primon-Barros et al 2015), que atuam como mecanismo de resistência à lise pelo complemento (Alderete et al 1995;Arroyo et al 2015). A importância do ferro para o parasito pode explicar, em parte, a maior prevalência da infecção entre as mulheres (Secor et al 2014), uma vez que elas têm em seu trato genital uma disponibilidade mais elevada desse íon, o que é relacionado ao fluxo menstrual.…”