PhD Discussions Sessions: Aida Baelo and Arnau Biosca

From the understanding to the treatment of biofilm wound infections

Wounds represent a very common and serious health problem worldwide. The exposure of host tissue to the external environment allows the proliferation of a broad variety of pathogenic microorganisms, causing severe infections that are difficult to eradicate, such as diabetic foot ulcers, burn and surgery wounds. Bacteria infecting wounds arrange themselves in polymicrobial communities known as biofilms. The features displayed by the biofilm hinder and delay the healing processes, as such bacterial communities exhibit higher resistance to antibiotics and higher ability to evade the immune response. The understanding of the interaction between the components of this microbial community within the host is essential in order to develop new healing strategies that target bacteria growing in wounds. However, classic culture methods do not allow the simultaneous co-culture of different bacterial species, or the study in a more-realistic infection site environment, where several host factors are presented.

We use a novel in vitro culture approach, optimizing a method to assess bacterial viability in a wound biofilm model. This in vitro multispecies biofilm model resembles the natural conditions present in wounds and allows us to study a Pseudomonas aeruginosa and Staphylococcus aureus co-culture, which are the predominant bacteria found in wounds. We show that P. aeruginosa and S. aureus reach an equilibrium in the wound-like environment, with both microorganisms replicating under these conditions. As replication is a crucial step to initiate an infection, we have first focused on the study of the differential role of the different P. aeruginosa Ribonucleotide Reductase (RNR) enzymes in bacterial growth within the wound biofilm model, as RNR are essential enzymes in DNA replication. Also, we use a set of biofilm-degrading enzymes targeting the wound biofilm so as to improve the antibiotic delivery in the local area of the infection site.

New antimalarial strategies and drug delivery systems based on nanotechnology

Despite the undeniable importance of malaria elimination on the global research agenda, available front-line drugs are rapidly loosing efficacy. Thus, alternative therapeutic strategies working through radically new mechanism are urgently needed. Also, improving the delivery of old antimalarial compounds to decrease their side effects and avoid resistance appearance is a priority. In this work we study two new antimalarial strategies and two new delivery systems.

First, using a combinational approach that uses experimental data and bioinformatics, we are exploring the cytotoxicity of protein aggregation on Plasmodium falciparum parasites as a new antimalarial strategy. He have observed and purified highly insoluble protein aggregates form living parasites from which we have selected a list of potential protein candidates to be tested as antimalarial agents. Also, we are investigating the antimalarial properties of Domiphen bromide (DMB) a highly hydrophobic compound predicted to inhibit a key enzyme of the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, absent in humans and found on the apicoplast organelle, a relic chloroplast of Plasmodium parasites.

Second, malaria eradication calls for strategies to reduce the transmission of the parasite from the human host to the mosquito vector. In this regard, and taking as a template the previously immunoliposome model developed in our group, we are now engineering a dual immunoliposome that targets gametocytes, the transmissible form of the parasite, and is loaded with two distinctive drugs. On the bilayer, the hydrophobic drug DMB is incorporated, and on the aqueous phase, the potent anti-gemetocidal compound, pyronoridine tetraphosphate, is actively encapsulated.

Finally, curcumin, a natural compound found in turmeric (Curcuma longa) presents promising antimalarial activity in vitro, but its low stability and intestinal absorption compromise their effectiveness in vivo. In this regard, we are working on the development of polymeric nanovectors for the improved abortion of curcumin in the intestinal mucosa.

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