Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications

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Nascimento Filho, Edson G. ; Vieira, Monica L. ; Teixeir, Aline F. ; Santos, Jademilson C. ; Fernandes, Luis G. V. ; Passalia, Felipe J. ; Daroz, Brenda B. ; Rossini, Amanda ; Kochi, Leandro T. ; Cavenague, Maria F. ; Pimenta, Daniel C. ; Nascimento, Ana L. T. O.

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 180, p. 8-pg., 2018-05-30.

Abstract

Leptospirosis is a severe disease that represents a significant burden to healthcare costs in the absence of prophylactic measures. There is no effective vaccine for humans. Although Leptospira genome sequencing has broadened our current knowledge of the life cycle and evolution of these bacteria, there is still much to be understood regarding the pathophysiological features of this organism. In tropical, underdeveloped regions, it is the predominant human disease. Pathogenic bacteria of the genus Leptospira are the etiological agents of leptospirosis. This review addresses the contributions made to our knowledge of leptospirosis based on proteomic strategies. We present here the advances made on several fronts in understanding the infectious agent Leptospira, from the initial 2D-gel electrophoresis proteomics approach to more advanced mass spectrometry (MS) technologies. This review provides an update on proteomic studies of Leptospira spp. and should be constructive in further investigations of these bacteria, in our fight against leptospirosis. Impact of our work: Leptospirosis is a severe disease that represents a significant burden to healthcare costs in the absence of prophylactic measures. There is no efficient vaccine for humans. This review addresses the contribution to Leptospira knowledge based on proteomic strategies. From the initial 2D- gel electrophoreses proteomics approach to more sophisticated mass spectrometry (MS) technologies, we have compiled most recent data of authors that have performed proteomic analyses on various approaches of leptospirosis, for instance: (i) authors that have assessed the infected rat urine, searching for markers; (ii) authors that have compared the proteome profiles of bacteria grown in vivo x in vitro; (iii) authors that have searched for vaccine candidates. This is a critical review on this subject pointing out future directions on Leptospira/leptospirosis research proteomics field, envisaging rational future work to increase our knowledge of these bacteria and help fight leptospirosis. (AU)

• FAPESP's process: 14/50981-0 - Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/01411-5 - Cloning, expression and characterization of HtrA proteins of Leptospira interrogans
• Grantee: Brenda Daroz
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/01102-2 - Biochemical and immunological evaluation of hypothetical surface proteins of Leptospira interrogans
• Grantee: Felipe José Passalia
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/01384-5 - Evaluation of the functional role of two Leptospira interrogans proteins in the adhesion process of the pathogen to the host
• Grantee: Leandro Toshio Kochi
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/04295-3 - Interaction of two Leptospira interrogans proteins to plasma and extracellular matrix components of the host
• Grantee: Maria Fernanda Cavenague Pereira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/11541-0 - Evaluation of the vaccine potential of antigenic fractions obtained in Leptospira interrogans serovar Copenhageni using hamsters as an animal model
• Grantee: Aline Florencio Teixeira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/06731-8 - Application of CRISPR-interference for elucidating leptospirosis pathogenesis and development of novel strategies for knockout mutant's obtainment
• Grantee: Luis Guilherme Virgílio Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral