Team
MEE
Team manager: RENDUELES GARCIA Olaya
Presentation
Our team combines computational and experimental approaches to study the ecology and evolution of microbial social interactions. We are interested in competition and cooperation, but also in horizontal gene transfer events mediated by mobile genetic elements such as plasmids and phages. We focus on surface structures, and namely the capsule, as a major driver of social interactions. As an experimental model, we use the gram-negative enterobacteria Klebsiella pneumoniae.
It is ubiquitous in nature, but also an opportunistic pathogen & a major multi-drug resistant (MDR) bacterium.
Project 1
Extracellular polysaccharidic capsules are a virulence factor of many bacteria, which also shapes gene flux and therefore, drives species evolution. This project stems from our novel observation that not all bacteria from a clonal population produce the same amount of capsule. Such phenotypic heterogeneity is an important bacterial feature to increase survival in fluctuating ecosystems, including upon antibiotic exposure, and impacting evolutionary adaptation.
Using Klebsiella pneumoniae as a model system, a nosocomial carbapenamase-producing pathogen causing lung, urinary and liver infections, we aim to: (i) characterize variation in capsule production at the single-cell level across strains and environments, (ii) investigate the mechanisms underlying this phenotypic heterogeneity, (iii) understand its effects on horizontal gene transfer and species evolution, and (iv) address the functional consequences of the cell-to-cell variation in capsule production regarding the infection process and persistence to antibiotic treatment.
This multidisciplinary project will address the phenotypic heterogeneity of a major virulence factor at different levels of cellular organization (from single cell to populations), across time scales (short to microevolution) and across various environments, including the mammalian host. It will provide an overview to how phenotypic heterogeneity in capsule production impacts evolvability and will contribute to identify the bacterial adaptive trends to better predict evolutionary outcomes in the wild and clinical contexts.
Project 2
The antibiotic resistance crisis is a global health threat accounting for over 1 million deaths worldwide. Yet, the development of new antibiotics and novel strategies has plummeted. Further, there is a the scarcity of studies taking into account ecological and evolutionary concepts and a lack of appropriate in vitro modelling of complex and 3D in-patient conditions. We posit that by harnessing microbial social interactions and organoid technology, we can develop rationally-designed antivirulence strategies to limit bacterial infection and spread of antibiotic resistance, whilst imposing less selective pressure for the emergence of resistance. The MicroINTERACT project combines computational approaches with experimental work in the fields of microbiology and cellular biology and places microbial social interactions at the core of biomedical research. microINTERACT will define new antivirulence strategies, whilst providing large opportunities for advances in our fundamental understanding of pathogen biology and derived infections.
Project 3
The escalating spread and emergence of antibiotic resistance (AMR) pose a serious threat to the decades-long progress in controlling infectious diseases. Plasmids play a pivotal role in driving the evolution and persistence of AMR, both in clinical and natural settings. Extensive studies have delved into the transfer and maintenance of plasmids carrying drug resistance genes in vitro conditions, particularly in the presence of antibiotics, and under various abiotic pressures like limited nutrients, osmolarity, and mutagens. However, there is a significant gap in our understanding of the impact of biotic pressures, such as bacterial predation, on the evolution and dissemination of resistance through plasmids. Bacterial predation is especially important in this context because bacterial predators like M. xanthus antibiotics to kill their prey. Thus, one of the selective pressures in nature for both the evolution and maintenance of resistance in natural microbial communities is likely to be the evolutionary arms race between antibiotic-producing predators and the plasmids conferring resistance to these antibiotics
Therefore, this project adopts an approach by placing bacterial predator-prey interactions at the forefront, offering a novel perspective on gene exchange dynamics. The investigation will integrate bioinformatics, population biology, molecular microbiology, chemical ecology, and evolutionary experiments to unravel the transfer rates and costs associated with plasmid maintenance in a relatively unexplored environment—the soil, a crucial reservoir for opportunistic pathogens.
– Haudiquet M, Le Bris J, Nucci A, Bonnin RA, Domingo-Calap P, Rocha EPC, Rendueles O.. Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency. Nature Communications 2024
– Nucci A, Janaszkiewicz J, Rocha EPC, Rendueles O. Emergence of novel non-aggregative variants under negative frequency-dependent selection in Klebsiella variicola. MicroLife 2023
– Nucci A, Rocha EPC, Rendueles O. Latent evolution of biofilm formation depends on life-history and genetic background NPJ Biofilms Microbiomes 2023
– D’Angelo F, Rocha EPC, Rendueles O. The Capsule Increases Susceptibility to Last-Resort Polymyxins, but Not to Other Antibiotics, in Klebsiella pneumoniae Antimicrob Agents Chemother. 2023
– Nucci A, Rocha EPC, Rendueles O.. Adaptation to novel spatially-structured environments is driven by the capsule and alters virulence-associated traits. Nature Communications 2022
– Rendueles O. Deciphering the role of the capsule of Klebsiella pneumoniae during pathogenesis: A cautionary tale. Mol Microbiol. 2020
Affiliation
