Identification and Functional Insights into New Phage Tail-Like Bacteriocins (PTLBs) Targeting Pseudomonas aeruginosa as new antimicrobials

The current health crisis caused by multidrug resistant (MDR) pathogens is one of the health problems of most concern globally. Infections caused by these pathogens, such as Pseudomonas aeruginosa , lead to high rates of complications, particularly in compromised patients such as cystic fibrosis (CF) patients. The need to counteract and minimize the forecast future impact has led to the rescue of phage therapy. The use of bacteriophages has important advantages, including highly specific targeting, self-amplification at the infection site, minimal disruption of the microbiome, safety and biocompatibility. However, the capacity of bacteria to escape these entities results in a form of resistance that compromises the effectiveness of the therapy. This involves the search for potential alternatives, such as the phage tail-like bacteriocins (PTLBs), also named as tailocins. These high molecular weight particles resemble the tail structure of bacteriophages and are characterized by the absence of genetic material, avoiding the development of resistance, one of the major handicaps associated with phage therapy. In this study, we detected 34 different PTLBs in 75 P. aeruginosa genomes, with different serotypes and sequence types, 11 of which were characterized as novel F-type PTLBs subtypes (F13-F24). Furthermore, we report that four selected PTLBs (R1, F15, F19, R3-F24) can deal with bacterial infection, with the R1 and the F15 PTLBs being the most efficient in clearing infection in vitro , yielding a survival rate of more than 75% in the Galleria mellonella larvae in vivo model. This reaffirms the potential of PTLBs to control P. aeruginosa infections, which can cause chronic infections in some patients, such as people with CF, due to its strong impact as a MDR bacterium.