## Materials and Methods
### Antimicrobial Agents  
Preparation of sterile stock solutions of tigecycline ([PERSON], Aprilia, LT, Italy) was performed according to the manufacturer's instructions. The antibiotic concentrations used in these experiments corresponded to tigecycline plasma concentrations achievable in humans [36].  
RIP and FS8 (Tyr-Ala-Pro-Trp-Thr-Asn-Ala-NH\({}_{2}\), Figure 1) were synthesized by the solid-phase method on a Rink amide-AM resin (1% DVB, 100-200 mesh, GLS Biochem Ltd., Shanghai, China) using the Fluorenylmethyloxycarbonyl (Fmoc) chemistry.  
_N_-\(\alpha\)-Fmoc-protected amino acids, 1-hydroxybenzotriazole (HOBt), _O_-Benzotriazole-_N_,\(N\),_N_-tetramethyl-uronium-hexafluoro-phosphate (HBTU) were purchased from GLS Biochem Ltd. (Shanghai, China); [PERSON] test kit, piperidine, \(N\),_N_-diisopropyllamine (DIPEA), triisopropylsilane (TIS), trifluoroacetic acid (TFA), dimethylformamide (DMF), methanol, and anhydrous diethyl ether, were purchased from Sigma-Aldrich (St. Louis, MO, USA). The following side-chain-protecting groups of the amino acids were used: tBu (Tyr and Thr), Boc (Trp), Trt (Asn).  
The peptide chain was elongated in consecutive cycles of deprotection and coupling. Before of each deprotection step the resin was washed with DMF (2\(\times\)), then the removal of the Fmoc groups was carried out adding 25% piperidine in DMF to the resin for 30 min. After the deprotection, the resin was washed with DCM (3\(\times\)) and DMF (3\(\times\)). The peptide elongation steps were performed with 3 equivalents of the protected amino acid, HOBt (3 equiv.), HBTU (3 equiv.), and DIPEA (6 equiv.) for 2 h. After the coupling, the resin was washed with DMF (3\(\times\)) and DCM (3\(\times\)) and the completeness of the reaction was confirmed by a negative Kaiser test of small sample of the resin. If the completion tests were positive, the coupling was repeated. After the final deprotection, the resin was washed with DMF (3\(\times\)), DCM (3\(\times\)), and MeOH (3\(\times\)), dried under vacuum and then stirred with a mixture of TFA:TIS:H\({}_{2}\)O (95:2.5:2.5) for 3 h. After this time, the resulting solution was filtered to remove resin beads and the peptide was precipitated with cold Et\({}_{2}\)O. The crude product was further purified using reversed phase HPLC on a Waters 600 HPLC (Waters Co., Milford, MA, USA) equipped with an X-Bridge(r) Prep BEH130 C18, 5 \(\upmu\)m (10 \(\times\)250 mm) column, with Waters 2996 PDA detector, using a solvent system of H\({}_{2}\)O/CH\({}_{3}\)CN (0.1% TFA) in the form of a linear gradient of CH\({}_{3}\)CN, from 5% to 30% in 10 min, from 30% to 35% in 15 min, from 35% to 90% in 5 min, and from 90% to 5% in 10 min, and a flow rate of 3 mL/min, yielding the peptide as trifluoracetate salts. The purity of the peptide was further analyzed by reverse phase HPLC using an X-Bridge BEH130 C18 (Waters Co., Milford, MA, USA), 5 \(\upmu\)m, 4.6 \(\times\) 250 mm column and a Waters 2996 PDA detector (280 nm and 220 nm) [30]. The identity of the peptide was confirmed by a MS spectra recorder using a LC-MS/MS system consisted of an LCQ (Thermo Finnigan, San Jose, CA, USA) ion trap mass spectrometer equipped with an electro-spray ionization (ESI) source (Table 3). The capillary temperature was set at 300 \(\,\)C and the spray voltage at 4.25 kV. The fluid was nebulized using nitrogen (N\({}_{2}\)) as both the sheath gas and the auxiliary gas.