Daniel López
Group Leader
Research summary
Our laboratory investigates the molecular mechanisms underlying the development of bacterial infections. We work at subcellular level studying the structural and biological role of the so-called bacterial lipid rafts and the role that these subcellular platforms play in the regulation of signaling in pathogens like Staphylococcus aureus. We also work at multicellular level, exploring how microbial communities evolve during an infection process. Our goal is to develop new strategies and antimicrobial therapies to eliminate infection diseases.
Publications
García-Fernández E, Koch G, Wagner RM, Fekete A, Stengel ST, Schneider J, Mielich-Süss B, Geibel S, Markert SM, Stigloher C, Lopez D. Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance. Cell. 2017 Nov 30;171(6):1354-1367.e20
García-Betancur JC, Goñi-Moreno A, Horger T, Schott M, Sharan M, Eikmeier J, Wohlmuth B, Zernecke A, Ohlsen K, Kuttler C, Lopez D. Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus. Elife. 2017 Sep 12;6. pii: e28023.
Schneider J, Klein T, Mielich-Süss B, Koch G, Franke C, Kuipers OP, Kovács AT, Sauer M and Lopez D. Spatio-temporal Remodeling of Functional Membrane Microdomains Organizes the Signaling Networks of a Bacterium. PLoS Genetics 2015; 11: e1005140 DOI: 10.1371/journal.pgen.1005140
Bramkamp M and Lopez D. Exploring the Existence of Lipid Rafts in Bacteria. Microbiology and Molecular Biology Reviews 2015; 79 (1) pp. 81-100. DOI: 10.1128/MMBR.00036-14
Koch G, Yepes A, Förstner KU, Wermser C, Stengel S, Modamio S, Ohlsen K, Foster K, Lopez D. Evolution of resistance to a last-resort antibiotic in Staphyloccocus aureus via bacterial competition. Cell 2014; 158:1060-1071 DOI: 10.1016/j.cell.2014.06.046
Our laboratory investigates the molecular mechanisms underlying the development of bacterial infections. We work at subcellular level studying the structural and biological role of the so-called bacterial lipid rafts and the role that these subcellular platforms play in the regulation of signaling in pathogens like Staphylococcus aureus. We also work at multicellular level, exploring how microbial communities evolve during an infection process. Our goal is to develop new strategies and antimicrobial therapies to eliminate infection diseases:
1. Single-cell level: Existence of lipid rafts in bacteria and development of anti-raft antibiotics to prevent infectious diseases.
One of the most sophisticated concepts in membrane organization is the proposed existence of lipid rafts. Membranes of eukaryotic cells organize signal transduction proteins into microdomains or rafts, that are enriched in particular lipids like cholesterol. Lipid rafts are important for the correct functionality of numerous cellular functions, and their disruption causes serious defects in several signal transduction processes. The assembly of lipid rafts in eukaryotes has been considered a fundamental step during the evolution of cellular complexity, suggesting that prokaryotes were too simple organisms to require such a sophisticated organization of their signaling networks. However, my group discovered that bacteria organize many signal transduction processes in functional membrane microdomains constituted by specific lipids. i.e. bacterial membranes contain lipid rafts similar to those found in eukaryotic cells. Importantly, the perturbation of bacterial lipid rafts inevitably leads to a potent and simultaneous impairment of all raft-harbored signal transduction pathways, which causes a potent inhibition of the infective potential in pathogenic bacteria. The discovery of lipid rafts in bacteria represents a new concept in biology that I address in my laboratory. I have consolidated S. aureus as working model in the study of bacterial lipid rafts to 1) understand the structural components involved in the assembly and maintenance of bacterial lipid rafts; 2) the biological role of bacterial lipid rafts in regulating infection-related process and 3) the feasibility of targeting the integrity of lipid rafts as a new strategy for anti-microbial therapy.
2. Community level: Cell-cell communication within staphylococcal biofilms
Antibiotics are the primary treatment for bacterial infections but the number of effective antibiotics is decreasing with the rising numbers of multi-drug resistant pathogens. However, the development of antibiotic resistance is also a naturally occurring process in bacteria, which is not exclusively restricted to clinically relevant species, which raises the possibility that the rising levels of antibiotic resistance in problem pathogens may also be influenced by competitive microbial interactions, similar to what occurs in natural environments. Bacterial colonization involves the formation of surface-associated aggregates or biofilms. Biofilm-encased cells are subjected to strong natural selection, as they compete for space and nutrients, which can shape microbial phenotypes and diversity. These conditions give rise to a heterogeneous population of genetically different bacteria that display characteristics that are relevant to understanding the progression of an infection. We investigate the possible factors involved in shaping the diversity of MRSA biofilms in which the pathogen could evolve new phenotypes that resist antibiotic treatment to ultimately elucidate how bacterial interactions play a role in microbial evolution and can serve to explain the diversification of key clinical phenotypes.
