Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Author(s):
    • Publication Information:
      Brazil
    • Abstract:
      More than 25% of human deaths are caused by infectious diseases, among which a large number are emerging and of zoonotic importance. Leptospirosis is considered one of the most important emerging zoonotic diseases. Its global distribution and its epidemic potential constitute a Public Health problem. It is estimated that approximately 1,03 million cases and 58,900 deaths from leptospirosis occur annually worldwide, but as a neglected disease, its actual prevalence is underestimated. Rattus norvegicus is the main reservoir associated with urban epidemics. Leptospires have the capacity to adhere to renal tubule cells which facilitates invasion and colonization. They also have mechanisms to evade the host's complement system. The identification of these mechanisms has been the object of research developed by several groups. Enolase and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) belong to the category of proteins known as moonlighting proteins. These encompass a group of multifunctional proteins. Enolases are cytosolic metalloenzymes that catalyze the conversion of 2-D-phosphoglycerate to phosphoenolpyruvate. Although they do not have a classic membrane anchor sequence, they are found on the surface of a variety of eukaryotic and prokaryotic cells, and have the capacity to interact with plasminogen. GAPDH is an enzyme of the glycolytic pathway responsible for the conversion of glyceraldehyde 3-phosphate to D-glyceryl 1,3-bisphosphate. Recent studies show that GAPDH has multiple functions independent of its role in energy metabolism. In this work we demonstrated that Leptospira GAPDH is located on the surface of the bacterium, and that both GAPDH and enolase interact with plasminogen, which is converted into its active form, plasmin, in the presence of the exogenous activator uPA. The capacity of plasmin-bound enolase to cleave physiological substrates was tested. The β-chain of fibrinogen was totally degraded, and vitronectin was partially cleaved into fragments of 61-64 kDa. Further, enolase interacts with the complement regulators C4BP and FH. Both regulators remain functional, acting as cofactors for Factor I on the degradation of C3b (FH) and C4b (C4BP). With regard to GAPDH, the date clearly show that plasmin bound to GAPDH degrades the α and β chains of fibrinogen as well as the 75-kDa isoform of vitronectin, in a time-dependent manner. Furthermore, in the presence of GAPDH, plasmin totally degraded C5 α-chain, but did not degrade C3b. Finally, our Far Western blot data reveal that GAPDH interacts with C1q, a key molecule of the classical pathway of the complement system, and also interacts with plasma fibronectin, and may therefore contribute to bacterial adhesion during host colonization. Briefly, in the present study we characterized two novel moonlighting proteins of Leptospira: enolase and GAPDH. The functional characterization of these proteins, as well as the identification of the host target molecules with which these proteins are capable of interacting, may contribute to the understanding of the mechanisms of invasion, dissemination and immune evasion used by pathogenic leptospires.
    • Number of References:
      79 ref.
    • Subject Terms:
      Public Health;Veterinary Science;Veterinary Science
    • Subject Terms:
    • Accession Number:
      animal reservoirs, bacterial infections, bacterioses, bacterium, brown rat, Norway rat, zoonotic infections
    • CABICODES:
      Prion, Viral, Bacterial and Fungal Pathogens of Humans (VV210) (New March 2000)
      Public Health Pests, Vectors and Intermediate Hosts (VV230) (New March 2000)
      Pathogens, Parasites and Infectious Diseases (Wild Animals) (YY700) (New March 2000)
      Biochemistry and Physiology of Microorganisms (ZZ394) (New March 2000)
    • Accession Number:
      9001-32-5; 37250-87-6; 9001-50-7; 9028-92-6; 9001-90-5; 9001-91-6
    • Publication Information:
      Thesis
    • Accession Number:
      20193371741
    • Copyright:
      ©2019 CAB International
  • Citations
    • ABNT:
      SOUZA, M. C. L. de. Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH. / Análise das funções moolighting de duas proteínas de Leptospira: enolase e GAPDH. 2018. Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, São Paulo; Brazil, 2018. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741. Acesso em: 20 set. 2020.
    • AMA:
      Souza MCL de. Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH. / Análise das funções moolighting de duas proteínas de Leptospira: enolase e GAPDH. Análise das funções moolighting de duas proteínas de Leptospira: Enolase e GAPDH. 2018:75. Accessed September 20, 2020. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741
    • APA:
      Souza, M. C. L. de. (2018). Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH. / Análise das funções moolighting de duas proteínas de Leptospira: enolase e GAPDH [Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia]. In Análise das funções moolighting de duas proteínas de Leptospira: Enolase e GAPDH (p. 75).
    • Chicago/Turabian: Author-Date:
      Souza, M. C. L. de. 2018. “Analysis of the Moonlighting Functions of Two Leptospira Proteins: Enolase and GAPDH. / Análise Das Funções Moolighting de Duas Proteínas de Leptospira: Enolase e GAPDH.” Análise Das Funções Moolighting de Duas Proteínas de Leptospira: Enolase e GAPDH. São Paulo; Brazil: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741.
    • Harvard:
      Souza, M. C. L. de (2018) Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH. / Análise das funções moolighting de duas proteínas de Leptospira: enolase e GAPDH, Análise das funções moolighting de duas proteínas de Leptospira: Enolase e GAPDH. Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia. Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741 (Accessed: 20 September 2020).
    • Harvard: Australian:
      Souza, MCL de 2018, ‘Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH. / Análise das funções moolighting de duas proteínas de Leptospira: enolase e GAPDH’, Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, São Paulo; Brazil, Análise das funções moolighting de duas proteínas de Leptospira: Enolase e GAPDH, p. 75, viewed 20 September 2020, .
    • MLA:
      Souza, M. C. L.de. “Analysis of the Moonlighting Functions of Two Leptospira Proteins: Enolase and GAPDH. / Análise Das Funções Moolighting de Duas Proteínas de Leptospira: Enolase e GAPDH.” Análise Das Funções Moolighting de Duas Proteínas de Leptospira: Enolase e GAPDH, Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, 2018, p. 75. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741.
    • Chicago/Turabian: Humanities:
      Souza, M. C. L. de. “Analysis of the Moonlighting Functions of Two Leptospira Proteins: Enolase and GAPDH. / Análise Das Funções Moolighting de Duas Proteínas de Leptospira: Enolase e GAPDH.” Análise Das Funções Moolighting de Duas Proteínas de Leptospira: Enolase e GAPDH. Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia, 2018. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741.
    • Vancouver/ICMJE:
      Souza MCL de. Analysis of the moonlighting functions of two Leptospira proteins: enolase and GAPDH. / Análise das funções moolighting de duas proteínas de Leptospira: enolase e GAPDH [Internet]. Análise das funções moolighting de duas proteínas de Leptospira: Enolase e GAPDH. [São Paulo; Brazil]: Universidade de São Paulo, Faculdade de Medicina Veterinária e Zootecnia; 2018 [cited 2020 Sep 20]. p. 75. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lhh&AN=20193371741