A lab study shows that a synthetic peptide called RP557, based on the human protein LL‑37, can kill carbapenem‑resistant Pseudomonas aeruginosa at much lower concentrations than LL‑37 itself and can break down its protective biofilm. When used together with standard carbapenem antibiotics, the peptides make the bacteria 4‑16 times more sensitive. The work is all in test‑tube experiments, so it isn’t ready for personal use yet, but it points to a potentially useful new antimicrobial approach.

<i>Pseudomonas aeruginosa</i> is a common bacterium in nosocomial infection. The biofilm-forming ability and antimicrobial resistance make <i>P. aeruginosa</i> biofilm infection refractory to patients requiring hospitalization, especially patients in the intensive care unit. Therefore, many alternative compounds have been developed. A newly synthesized peptide, RP557, derived from human cathelicidin LL-37, was evaluated for its antimicrobial and antibiofilm effect toward carbapenem-resistant <i>P. aeruginosa</i> (CRPA). The results showed that regardless of the resistance to carbapenems, the minimal inhibition concentrations of RP557 and LL-37 against <i>P. aeruginosa</i> were 32 &#xb5;g/mL and 256 &#xb5;g/mL, respectively. Both RP557 and LL-37 significantly reduced the <i>P. aeruginosa</i> biofilm mass at subMICs, while subMICs of carbapenems induced biofilm formation. RP557 could also remove approximately 50% of the mature biofilm at a concentration of 64 &#xb5;g/mL, while 256 &#xb5;g/mL LL-37 was needed to remove it. A quarter MIC of RP557 and LL-37 was used together with carbapenems (ertapenem, imipenem, and meropenem). The results show that both RP-557 and LL-37 might increase the susceptibility to CRPA by 4-16 times. Significant gene expression level changes were observed in RP557- or LL-37-treated CRPA. Confocal images showed that biofilm structures and biofilm cell viability were significantly reduced in the LL-37- or RP557-treated groups. Therefore, RP557 and its structural origin, LL-37, could be potential treatments for carbapenem-resistant <i>P. aeruginosa</i> infection, especially for chronic biofilm infection. IMPORTANCE <i>Pseudomonas aeruginosa</i> is one of the major pathogens of nosocomial infection. Combined its biofilm-forming ability with carbapenem-resistance, it is hard to handle <i>P. aeruginosa</i> infection, especially for patients requiring hospitalization. Antimicrobial peptide is a type of potential compound for bacterial infection treatment. Among these, RP557 was found effective in inhibiting biofilm previously. By assessing its effect on both carbapenem-resistant <i>P. aeruginosa</i> planktonic cells and biofilm, our results offered a potential treatment for carbapenem-resistant <i>P. aeruginosa</i> infection. It could be helpful to treat severe nosocomial infection related to carbapenem-resistant bacteria and increase the patients' survival rate.