Tackling Bacterial Disease With Multivalent, Surface-Targeted Nanostructures

Our group holds several research lines focused on the search for novel antimicrobials and on the study of protein immobilization strategies for biomedical applications. To do so, our expertise encompasses the biophysical study of protein structure, folding and engineering, as well as the employment of microbiology, nanobiotechnology and biopolymer techniques.

a) Combating the respiratory pathogen Streptococcus pneumoniae (pneumococcus). This bacterium is a major responsible, among others, of community-acquired pneumonia, meningitis and otitis media. It causes more than 1 million deaths worldwide, especially infants and people over 65, and it has been described as one of the major co-infectants with SARS-CoV-2, which complicates the treatment of the coronavirus disease. Moreover, S. pneumoniae presents serious antimicrobial resistance threats, and present vaccination only covers a part of all serotypes - hence the need of search for novel antipneumococcal therapies.

b) We have identified novel lytic enzymes ("enzybiotics") that degrade the cell wall of Gram-negative pathogens such as Pseudomonas aeruginosa. An advantage of the enzybiotic system is that its efficiency is extremely high, leading to a truly sterilization of the medium, together with its remarkable specificity, and that the probability of appearance of resistances is low due to to the conserved nature of the substrate (the cell wall). We are now investigating the engineering of these enzymes to increase their activity, and the use of permeabilizing peptides, either fused to the enzybiotic or immobilized in nanoparticles to gain access to the cell wall through the outer membrane.

We are willing to collaborate, in any of the different MSCA schemes, in a project dedicated to fight antimicrobial resistance with a molecular approach. We provide expertise in protein structure, folding and design, and a knowledge on bacterial cell wall as novel targets for antimicrobials.