Unraveling Challenges in Multidrug-Resistant Bacteria Colonization: From Microbiota Dynamics to Therapeutic Interventions

• Grant number: 24/14957-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Cristina Gales
• Grantee: Ághata Cardoso da Silva Ribeiro
• Supervisor: Alessio Fasano
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Massachusetts General Hospital, United States
• Associated to the scholarship: 23/14561-6 - Differences among healthy, sick and MDR colonized patient's gut microbiome and the effect of Fecal Microbiota Transplantation as a therapeutic strategy to restore the gut microbiome., BP.PD

Abstract

Colonization with multidrug-resistant (MDR) bacteria significantly raises the risk of developing severe MDR infections, associated with higher mortality and morbidity rates, especially in vulnerable groups susceptible to intestinal disruption and translocation. The understanding of intestinal microbiota in colonized patients and conditions facilitating successful MDR colonization remains limited. Interactions between microbiota, colonizers, hosts, and immune responses to colonization are poorly understood. Triggers promoting intestinal translocation from colonization to infection are unknown. Effective therapeutic interventions to address colonization and prevent subsequent infections are lacking. Based on these premises, our first goal is to analyze intestinal microbiota in patients colonized by Klebsiella pneumoniae Carbapenemase (KPC) and/or New-Delhi Metall-¿-lactamase (NDM)-producing K. pneumoniae via metagenomic analysis of fecal samples. Using the Human Intestinal Organoid-Derived Epithelial Monolayer Model (HIODEM) preclinical model under varied nutritional conditions, we aim to simulate colonization patterns and observe alteration in the instestinal microbiota by metagenomics. This will elucidate K. pneumoniae interactions with microbiota, hosts, and intestinal tissue, exploring how nutrition affects colonization and infection. We also seek to identify triggers for development of K. pneumoniae infection following intestinal colonization by this pathogen. Our ultimate goal is to use the organoide model, HIODEM, to test the use of FMT combined or not with specific bacteriophages as an alternative for decolonization targeting KPC- and/or NDM-producing K. pneumoniae.