摘要：SummaryAntibiotic 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-RasGAP317-326is 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 thatEscherichia coliandPseudomonas aeruginosarespond to TAT-RasGAP317-326by 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 TAT-RasGAP317-326, which may help developing antimicrobial treatments based on this peptide.Graphical abstractDisplay OmittedHighlights•Antimicrobial activity of TAT-RasGAP317-327is affected by medium composition•Peptide exposure induces metabolic and stress responses•Cell surface modifications influence peptide antimicrobial activity•Resistance to TAT-RasGAP317-327peptide does not lead to multidrug resistanceBiochemistry; Peptides; Microbiology
