Short Synthetic Lipopeptides C16-KK-NH2 and (C10)2-KKKK-NH2 Enhance the Activities of Erythromycin and Tetracycline Against ESKAPE Pathogens

Background: ESKAPE constitutes a group of six nosocomial bacteria that can evade available antimicrobials due to their great potential to develop multi-drug resistance and biofilm-forming abilities. These pathogens often cause hospital-acquired infections and pose a serious threat to public health. The search for efficient innovative therapeutic strategies to fight ESKAPE bacteria have been intensively investigated topics. One promising approach to fight resistant pathogens and their biofilms is combination therapy, which allows the effectiveness against microorganisms to be increased while reducing the applied concentrations and risks of potential unwanted side effects. Objectives: The object of the study was to determine if there is an interaction of short lipopeptides ((C10)2-KKKK-NH2, C16-KK-NH2) together with erythromycin and tetracycline against pathogens of the ESKAPE group (Acinetobacter baumannii, Enterobacter aerogenes, Enterococcus faecium Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus). Methods: The checkerboard assay was used to examine the activity of compounds applied in combinations against ESKAPE strains in planktonic cells and toward biofilms formed by Staphylococcus aures and Pseudomonas aeruginosa. Results: The lipopeptides demonstrated a great potential of their application as additives to conventional antimicrobials against Gram-negative bacteria, including microorganisms within biofilms.