Ecology and Evolution of Plasmid-Mediated Antibiotic Resistance in Human Gut Microbiota
Main funder
Funder's project number: 354982
Funds granted by main funder (€)
- 707 671,00
Funding program
Project timetable
Project start date: 01/09/2023
Project end date: 31/08/2027
Summary
The growing emergence of antibiotic resistance is an alarming threat to modern healthcare. In natural and clinical environments, bacteria acquire antibiotic resistance via horizontally transferred conjugative plasmids which are often provided with accessory traits, including antibiotic resistance genes. As plasmids operate as mobile genetic vehicles to disseminate resistance traits between individual bacteria and across microbial communities, they are considered a key player in the evolution of antibiotic resistance. Healthy human gut microbiota naturally carries various resistance genes, which cause no harm to the human host per se, however, fecal carriage of multidrug-resistance is a potential risk for infection. Antibiotic therapies are used as treatments for many common diseases but besides that they are known to alter the structure of microbial community, they also promote the emergence of resistant bacteria in the gut. Further, bacteria can disseminate resistance to adjacent cells via conjugation even under antibiotic exposure in vitro. On the other hand, bacteria have also developed mechanisms for defending against genetic invaders, such as plasmids, which are not always beneficial. Microbial single-cell technologies can be utilized for detecting resistance plasmids and identifying their bacterial hosts within complex microbial communities at single-cell resolution. This work exploits single-cell technologies to explore the evolution of conjugative resistance plasmids and investigate the role natural CRISPR defense systems in controlling plasmid dispersal in microbial communities during antibiotic treatment. The study will provide a more profound view on the resistance plasmid dynamics in human gut microbiota and emphasize the role of CRISPR systems in plasmid dispersal within clinical environments, which is a highly under-explored research area.
