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Activity Funded

Fostering the development of new probiotic therapeutic approaches for the tretament of candidiasis through the exploration of lactobacilii-Candida interference mechanisms

Explorando a interferência probiótica entre lactobacilos e Candida para potenciar o desenvolvimento de novas terapias antifúngicas

Reference
PTDC/BIA-MIC/31515/2017
Project Start Date
2018-10-01
Project End Date
2022-09-30
Principal Investigator
Coinvestigator
Scientific Area
Natural sciences
Funding Program
Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017

Abstract

Candida albicans (Ca) and C. glabrata (Cg) are common human commensals but under certain conditions can cause mucosal infections and, in more serious cases, life-threatening systemic candidiasis. The essential role of commensal microflora in shaping the equilibrium between health and disease through the control of pathogens is being increasingly recognized as metagenomics booms. Lactobacilii predominate in the vaginal microbiome and in the GI tract and this predominance was linked with health of these niches. Indeed, in vitro vaginal lactobacilii strains were found to inhibit growth of Candida while indigenous gut lactobacilii species were shown to prevent commensal Ca populations from disseminating through the bloodstream. The mechanisms underlying this interference between lactobacilii and Candida are poorly understood. Our project aims to explore this gap in knowledge to open the door to new intervention therapies aiming to tip the balance in favor of the commensal microflora. In a time of awareness due to the constant emergence of Candida strains resistant to currently used antifungals, the development of therapeutic approaches based on alternative targets is essential. The effect in growth and morphology of Ca or Cg upon co-cultivation with vaginal/intestinal lactobacilii will be gathered in a variety of relevant environmental conditions. The impact of the co-cultivation in virulence of Ca/Cg is the objective of Task2. Ex-vivo infection models and Galleria mellonela, will be used to study how lactobacilii modulate virulence of Candida. The transcriptome-wide alterations occurring in a co-culture between Candida/lactobacilii and intestinal/vaginal cells will be studied on Task4, while on Task5 the genes mediating survival of Candida and of lactobacilii in the presence of each other will be identified. This information clears the picture on Candida/lactobacilii interaction and provides a new set of targets for the design of new antifungals. Since adaptation to the vaginal or the GI environment is likely to result in significant alterations in the genomic repertoire of the colonizing populations, the genome sequence of set of vaginal Ca, Cg or lactobacilii strains will be obtained and mined. In the final task of the project the knowledge obtained will be integrated to select a set of modifications that could be performed in the indigenous vaginal or intestinal lactobacilii species to increase their anti-Candida potential and their residence time in the infection sites. By taking into account the effects exerted by commensal lactobacilii our approach significantly advances the current understanding of Candida spp. mucosal and systemic infections. The anticipated industrial application of the results through the production of new pharmaceuticals and/or nutraceuticals fosters innovation in national Pharma and Food industries

Institutions

Main Institutions

  • Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento (IST-ID)

Other Institutions

  • Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento (IST-ID)
  • Universidade do Minho (UMinho)

Funding 238.325,62 €

Fundação para a Ciência e a Tecnologia (FCT) - Portugal

238.325,62 €
  • 2018-01-01 a 2025-12-31
  • PTDC/BIA-MIC/31515/2017