regional hub for collaboration between Central America and the - - PowerPoint PPT Presentation

Center for Research in Tropical Diseases (CIET): a regional hub for collaboration between Central America and the Institut Pasteur International Network

Esteban Chaves Olarte, Universidad de Costa Rica

MEETING OF THE INSTITUT PASTEUR INTERNATIONAL NETWORK (RIIP) – AMERICAN REGION, July 2019

University of Costa Rica Faculty of Microbiology/CIET

50 Active projects 39 associated researchers 291 Scientific publications, 1 patent (10 years) Funding from national and international agencies Strong links to post graduate programs 40500 students 545 academic programs 1400 research programs 284 international agreements Ranking QS: 19 in Latin America

Research interests

Clostridium difficile Brucelosis Arboviruses Malaria Xylella fastidiosa Cancer

International cooperation and networking 1989-2013 NeTropica

Javier Pizarro, Institut Pasteur

2019-20XX

Diseases caused by Clostridium difficile

Clinical spectrum Pathogenesis

Genetic diversity among C. difficile strains

Core genome, 30%. High plasticity

He et al., PNAS 2010 Scott et al., JCM 2006

Variation in virulence potential Hipervirulent phenotype Fluoroquinolone resistance (gyrA mutation) Binary toxin tcdC deletion Increased TcdA and TcdB Increased sporulation TcdB variants

NAP1/027 genotype

Outbreak of C. difficile in a Costarican hospital

45% NAP1 31% NAPCR1

(JCM, 2015, 53:1216)

Clinical presentation Virulence in hamster

NAP1 and NAPCR are unrelated virulent C. difficile strains

NAPCR NAP1

(JCM, 2015, 53:1216)

Hipervirulent phenotype Fluoroquinolone resistance (gyrA mutation) Binary toxin tcdC deletion Increased TcdA and TcdB Increased sporulation TcdB variants

NAP1 NAPCR

Hipervirulent phenotype Fluoroquinolone resistance (gyrA mutation) tcdC deletion (no point mutation)

NAPCR does not hyper produce toxins HIPOTHESIS: NAPCR secretes additional molecules that synergize the action of the toxins

Toxin free supernatants from NAPCR strain are proinflammatory

Toxins + Toxins -

Toxin free supernatant from NAPCR has increased proinflammatory activity Emerging virulent strain Resistant to fluoroquinolone Novel virulence mechanism

Other contributions in C. difficile

• J. Biol. Chem. 2011, 286: 24977-86

Caspase activatable-GFP (CA-GFP) Molecular sensors to detect flavivirus multiplication

Arias-Arias et al. (2017) Unpublished data

The NS3A-GFP/Flavi reporter becomes fluorescent upon cleavage by DENV/ZIKV proteases in cell-free system

tGFP/control:

The NS3A-GFP/Flavi reporter becomes cleaved and fluorescent into stably transduced mammalian cells upon flaviviral infection

Arias-Arias et al. (2018) Unpublished data

Acknowledgments

Carlos Quesada Cesar Rodríguez Jorge Arias Carlos Chacón Pamela Altamirano Eugenia Corrales

Obrigada!!!!