Antibiotic resistance is a major challenge in the management of bacterial infections. One of the goals of research in this field is to develop alternative antimicrobial strategies to antibiotics, such as anti-virulence drugs, which interfere with the ability of bacteria to cause damage or disease, or adjuvant molecules, which re-sensitize resistant bacteria to antibiotics. 
Bacterial virulence and antibiotic resistance can be regulated by small RNA fragments (sRNAs) produced by the bacteria themselves. A small sRNA from Pseudomonas aeruginosa called ErsA has previously been identified: the absence of this RNA reduces the virulence of the bacterium.  
Thanks to previous projects funded by FFC Ricerca (FFC#13/2015, FFC#14/2016, FFC#10/2020 and FFC#14/2021), molecules capable of inhibiting ErsA, called Peptide Nucleic Acids (PNA), have been developed. 

In this project, the researchers tested the different PNAs on multidrug-resistant P. aeruginosa cells from biological samples, in the presence of the antibiotic meropenem, to evaluate their effectiveness in re-sensitizing the bacterium to the antibiotic. By administering the PNAs to the bacteria in vitro, the researchers obtained bacteria that were once again sensitive to meropenem. 

In subsequent experiments, the researchers observed that some of these bacteria were able to regain resistance to the antibiotic; however, this resistance was lower than that of bacteria not treated with PNAs, and the virulence characteristics of the bacteria were not restored.

The analysis was then extended in vivo to an animal model in collaboration with the CFaCore service of FFC Ricerca: the in vivo study is still ongoing, but has shown that the PNAs tested attenuate the pathogenicity of the bacteria tested.

The next step will be to refine these molecules and further evaluate the effect of the PNA-meropenem combination.
The PNAs developed by this project could become new antimicrobial drugs for use in cases of infection by antibiotic-resistant P. aeruginosa.