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LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro.
Kraeva, Natalya; Lestinová, Tereza; Ishemgulova, Aygul; Majerová, Karolina; Butenko, Anzhelika; Vaselek, Slavica; Bespyatykh, Julia; Charyyeva, Arzuv; Spitzová, Tatiana; Kostygov, Alexei Yu; Lukes, Julius; Volf, Petr; Votýpka, Jan; Yurchenko, Vyacheslav.
Affiliation
  • Kraeva N; Life Sciences Research Centre, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.
  • Lestinová T; Department of Parasitology, Faculty of Science, Charles University, 12844 Prague, Czech Republic.
  • Ishemgulova A; Life Sciences Research Centre, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.
  • Majerová K; Department of Parasitology, Faculty of Science, Charles University, 12844 Prague, Czech Republic.
  • Butenko A; Life Sciences Research Centre, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.
  • Vaselek S; Biology Centre, Institute of Parasitology, Czech Academy of Sciences, 37005 Ceské Budejovice (Budweis), Czech Republic.
  • Bespyatykh J; Department of Parasitology, Faculty of Science, Charles University, 12844 Prague, Czech Republic.
  • Charyyeva A; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
  • Spitzová T; Life Sciences Research Centre, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.
  • Kostygov AY; Department of Parasitology, Faculty of Science, Charles University, 12844 Prague, Czech Republic.
  • Lukes J; Life Sciences Research Centre, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.
  • Volf P; Zoological Institute of the Russian Academy of Sciences, 199034 St. Petersburg, Russia.
  • Votýpka J; Biology Centre, Institute of Parasitology, Czech Academy of Sciences, 37005 Ceské Budejovice (Budweis), Czech Republic.
  • Yurchenko V; University of South Bohemia, Faculty of Sciences, 37005 Ceské Budejovice (Budweis), Czech Republic.
Pathogens ; 8(4)2019 Nov 17.
Article in En | MEDLINE | ID: mdl-31744234
ABSTRACT
Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host's phosphorylation profile or signal transduction pathways. Multiple phosphatases and kinases from diverse bacterial pathogens have been implicated in human infections before. In this work, we have identified and characterized the dual specificity protein/lipid phosphatase LmDUSP1 as a novel virulence factor governing Leishmania mexicana infection. The LmDUSP1-encoding gene (LmxM.22.0250 in L. mexicana) has been acquired from bacteria via horizontal gene transfer. Importantly, its orthologues have been associated with virulence in several bacterial species, such as Mycobacterium tuberculosis and Listeria monocytogenes. Leishmania mexicana with ablated LmxM.22.0250 demonstrated severely attenuated virulence in the experimental infection of primary mouse macrophages, suggesting that this gene facilitates Leishmania pathogenicity in vertebrates. Despite significant upregulation of LmxM.22.0250 expression in metacyclic promastigotes, its ablation did not affect the ability of mutant cells to differentiate into virulent stages in insects. It remains to be further investigated which specific biochemical pathways involve LmDUSP1 and how this facilitates the parasite's survival in the host. One of the interesting possibilities is that LmDUSP1 may target host's substrate(s), thereby affecting its signal transduction pathways.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Country/Region as subject: Mexico Language: En Journal: Pathogens Year: 2019 Type: Article Affiliation country: Czech Republic

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Country/Region as subject: Mexico Language: En Journal: Pathogens Year: 2019 Type: Article Affiliation country: Czech Republic