Antibiotic resistance has been a major global health threats in the century, as increasing bacterial strains have become resistant to first-line antibiotic. Moreover, according to the report of World Health Organization (WHO), carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) are two of the most threatening strains in the world. Although antimicrobial peptide (AMP) offers a promising solution by killing bacteria through membrane disruption, which reducing the likelihood of resistance development, high concentrations of AMPs may induce side effects (e.g., kidney failure). To address this issue, double-cooperative effect has been attracting attention. Double-cooperative effect is the phenomenon which will enhance the effectivity of killing bacteria by mixing two different kind of AMP and reduce cytotoxicity to host cell simultaneously. In this research, we are going to develop and evaluate different kind of AMP combinations built around polymyxin B and colistin. We determine AMP combinations effectivity against the target bacteria using minimum inhibitory concentration (MIC) assay and checkerboard assay, and we assess cytotoxicity with fluorescence recovery after photobleaching (FRAP), MTT assay, and live/dead assay. Under the tested condition, we observed that the combination of polymyxin B with LL-37, and the combination of colistin with LL-37 showed limited inhibition of Acinetobacter calcoaceticus growth. Guided by the result, we are systemically evaluating additional AMP combination to enhance efficacy while minimizing host cytotoxicity, advancing AMP-based combinations against CRKP and CRAB.
Weng et al. (Sun,) studied this question.