Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DelNAM (Strengthening the Research Area of Delivery of Nucleic acid mimics (NAMS) into bacteria to fight the antibiotic crisis)

Teaser

Bacterial resistance to antibiotics poses a threat to the global public health, being already responsible for thousands of annual deaths globally and expected to kill more than cancer by 2050 if no solution is encountered. However, the development of novel antibiotics has...

Summary

Bacterial resistance to antibiotics poses a threat to the global public health, being already responsible for thousands of annual deaths globally and expected to kill more than cancer by 2050 if no solution is encountered. However, the development of novel antibiotics has proven to be a challenge for pharmaceutical companies due to the rapid acquisition of resistance by bacteria.
Nucleic Acid Mimics (NAMs) may be the answer to this problem, since they can be designed to recognize and block key bacterial genes. Therefore, depending on the target, NAMs can be used to kill bacteria or to restore bacterial susceptibility to antibiotics, provided they can penetrate bacteria and reach their targets. The penetration of NAMs is, however, limited by the complex bacterial envelope composed of several layers that surround the bacterial cells. As a result, the NAMs need to be delivered across the bacterial envelope.
The DelNAM project aims to develop an innovative solution to fight and solve the crisis of bacterial resistance to antibiotics, through the delivery of NAMs into bacteria. In addition, DelNAM aims to position the consortium as leaders in the application of NAMs and delivery vehicles to combat bacterial resistance to antibiotics, raise public awareness concerning this problem, and train the Portuguese institution’s research staff in emergent technologies and interface science areas.

Work performed

During the period covered by the report, DelNAM’s team has defined a long-term research strategy in the scientific area of NAMs delivery. This strategy encompasses the exchange of knowledge and researchers between the consortium’s institutions and the investment in technological capacity, in addition to the active commitment to dissemination and exploitation, and to the search for new funding opportunities. The application of this strategy has been crucial to develop FEUP’s innovation management and scientific production capabilities. A PhD student has already been to a partner institution in order to take advantage of their know-how and technical capabilities, and this type of exchange will continue to be encouraged and of interest to the development of the project. Additionally, several efforts have been made to invest in new equipment, to benefit from the techniques available across the consortium, and to set new collaborations, in order to gain access to the methods that are not yet available within the consortium.
The group has organized and participated in several events, with the objective of disseminating results and increasing DelNAM’s contact network. Furthermore, several companies and research groups have been contacted in order to promote future collaborations, aiming to improve the exploitation of the project and its results, as well as seeking a future translation into the industry. The team has also been responsible for regular communications on social media platforms and the project’s website, with the intention to maximize DelNAM’s impact, reaching not only the scientific community but the general public as well.
In order to improve the researchers’ skills in the study area, the group has developed and supervised research projects, as well as encouraged the participation in external conferences, to promote the attainment of shared knowledge. Additionally, several training actions have been organized to facilitate improvement of the members’ competences in science communication and knowledge valorization.
Lastly, the team has been successful in the monitoring and the coordinating of tasks, putting corrective measures in practice when necessary, and has ensured compliance with the set-out ethics requirements.

Final results

In terms of scientific progress, the researchers have been working to apply fluorescence recovery after photobleaching (FRAP) in the evaluation of the diffusion of NAMs in the cytoplasm of bacteria for the first time, in order to gain better insight into the underlying internalization mechanisms. Additionally, the group has been studying the interaction mechanisms between NAMs and certain carriers, such as fusogenic cationic liposomes, so as to facilitate their loading. The team at FEUP has taken advantage of specialized techniques available within the consortium, like Fluorescence Correlation Spectroscopy (FCS) and Nanoparticle Tracking Analysis (NTA), to evaluate the stability of the NAM/liposome complexes.
In terms of the scientific and social impact, a number of measures have already taken effect. Several publications, prepared in the scope of the DelNAM project, have been accepted and are currently in press. Additionally, researchers have been integrated in the UPORTO team under the DelNAM research area, under research grants or doctoral programs, leading to an increase in their qualifications and the enhancement of the research & development activities at UPORTO. Social networks and the group’s events have been used as a way to raise awareness towards antimicrobial resistance not only in the scientific community, but in the general public as well. While measures such as intellectual property protection and the creation of new business models are out of reach for now, given the current technology readiness level (TRL) of the project, these goals remain in DelNAM’s horizon. As such, a particular effort has been made to expand the DelNAM network and to participate in actions related to the valorization of results, towards facilitating the transition of the project’s research to a marketable product to fight antimicrobial resistance.

Website & more info

More info: http://www.delnam.com/.