TY - JOUR T1 - Bacterial surface properties influence the activity of the TAT-RasGAP<sub>317-326</sub> antimicrobial peptide JF - bioRxiv DO - 10.1101/2020.10.02.321802 SP - 2020.10.02.321802 AU - Maria Georgieva AU - Tytti Heinonen AU - Alessandra Vitale AU - Simone Hargraves AU - Senka Causevic AU - Trestan Pillonel AU - Leo Eberl AU - Christian Widmann AU - Nicolas Jacquier Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/05/2020.10.02.321802.abstract N2 - Antibiotic resistance is an increasing threat for public health, underscoring the need for new antibacterial agents. Antimicrobial peptides (AMPs) represent an alternative to classical antibiotics. TAT-RasGAP317-326 is a recently described AMP effective against a broad range of bacteria, but little is known about the conditions that may influence its activity. Using RNA-sequencing and screening of mutant libraries, we show that Escherichia coli and Pseudomonas aeruginosa respond to TAT-RasGAP317-326 by regulating metabolic and stress response pathways, possibly implicating two-component systems. Our results also indicate that bacterial surface properties, in particular integrity of the lipopolysaccharide layer, influence peptide binding and entry. Finally, we found differences between bacterial species with respect to their rate of resistance emergence against this peptide. Our findings provide the basis for future investigation on the mode of action of this peptide and its potential clinical use as an antibacterial agent.Competing Interest StatementThe authors have declared no competing interest. ER -