Projects

One of the greatest challenges in the modern world is the growing threat of antibiotic-resistant pathogens. To combat this issue, the European Union has banned the use of antibiotics for animal growth promotion. A promising solution lies in understanding microbial interactions and the strategic application of beneficial microbes to combat resistant pathogens. Microbial interactions are key drivers of human, animal, and environmental health.

Probiotics—live microorganisms that confer health benefits to the host—are considered a sustainable and environmentally friendly solution to fight antibiotic resistance. However, a deep understanding of their interactions with pathogens and hosts remains lacking. These studies are especially important given the increasing demand for probiotics in human nutrition and animal husbandry.

This project, with the acronym COMPATPROBs (Competition between Pathogen and Probiotic B. subtilis), will address key unanswered questions, including:

a) What molecular cues and responses are triggered when a pathogen encounters a probiotic in a low-nutrient environment?

b) Can probiotics influence the antibiotic sensitivity of resistant pathogens?

c) Do pathogens develop resistance to probiotics, and if so, how?

d) How do probiotics behave at intestinal epithelial barriers and in vivo, and where do they localize?

COMPATPROBs builds on our recent discoveries that the patent-protected strain Bacillus subtilis PS-216 inhibits the growth of foodborne pathogens in vitro by secreting antibiotic bacillaene and positively influences the growth and immune status of broilers in vivo . These findings, along with preliminary data detailed in the proposal, form the foundation of this project. The main objective is to further characterize the mechanisms driving interactions between Bacillus subtilis PS-216 and Salmonella Typhimurium in vitro and extend the research to the in vivo murine model. This will be achieved through six work packages:

WP1: Preparation of specific mutants and recombinant strains, along with optimization of selected model systems.

WP2: Characterization of competition-sensing mechanisms in nutrient-limited environments.

WP3: Investigation of the probiotic’s role in modulating pathogen sensitivity to antibiotics.

WP4: Assessment of the stability of the probiotic’s antagonistic effects against Salmonella during experimental evolution.

WP5: Analysis of pathogen-probiotic interactions and their implications for the host using an intestinal epithelial barrier model and a mouse infection model.

WP6: Project organization and dissemination of findings.To achieve these goals, COMPATPROBs brings together the expertise of their research groups from UL-BF and the expertise from NIB (National Institute of Biology):

The MICRO – BF group, specializes in social microbiology, comparative genomics, mutant and reporter strain construction, experimental evolution, and high-resolution confocal microscopy.

The BioNANO- BF group, provides expertise in intestinal epithelial barrier models, immune responses, and scanning electron microscopy.

The Center for Laboratory Animals and Genomics- BF, offers expertise in mouse infection models, host response measurements, and in vivo imaging.

The BioTEHSystem group (NIB) provides expertise in transcriptomicsThe strength of the COMPATPROBs is the complementary expertise of four internationally recognized and experienced teams and hypothesis-driven proposal that aims to:

A) Bridge the gap in understanding the complex regulatory pathways and molecular cues triggered by interspecies competition.

B) Explore novel approaches to enhance the sensitivity of antibiotic-resistant pathogens to antibiotics used in Salmonella treatment.

C) Generate new knowledge on microbe-pathogen and microbe-host interactions in both in vitro and in vivo models, contributing to developing safer, more effective, and reliable probiotics while providing potential strategies to combat antibiotic resistance.

SICRIS