Maria Georgieva, Tytti Heinonen, Alessandra Vitale, Simone Hargraves, Senka Causevic, Trestan Pillonel, Leo Eberl, Christian Widmann and Nicolas Jacquier
Antibiotic resistance is an increasing threat for public health, underscoring theneed for new antibacterial agents. Antimicrobial peptides (AMPs) represent analternative to classical antibiotics. TAT-RasGAP317-326is a recently describedAMP effective against a broad range of bacteria, but little is known about the con-ditions that may influence its activity. Using RNA-sequencing and screening ofmutant libraries, we show thatEscherichia coliandPseudomonas aeruginosarespond to TAT-RasGAP317-326by regulating metabolic and stress response path-ways, possibly implicating two-component systems. Our results also indicate thatbacterial surface properties, in particular integrity of the lipopolysaccharidelayer, influence peptide binding and entry. Finally, we found differences betweenbacterial species with respect to their rate of resistance emergence against thispeptide. Our findings provide the basis for future investigation on the mode ofaction of TAT-RasGAP317-326, which may help developing antimicrobial treat-ments based on this peptide.