Background: Carbapenem-resistant Acinetobacter baumannii (A. baumannii) was on the top
of the list of the most threatening bacteria published by the WHO in 2017. Antisense oligonucleotides
(ASOs) based therapy is a promising strategy for combating Multi-Drug Resistant (MDR) bacteria because
of its high specificity, easy design and lower induction of resistance, but poor cellular uptake by
bacteria has restricted the further utilization of this therapy.
Methods: Here, we used CADY, a secondary amphipathic peptide of 20 residues that could successfully
carry siRNA into mammalian cells, to prepare CADY/ASOs nanoparticles (CADY-NPs) targeting acpP
(encoding acyl carrier protein), and evaluated the uptake features, the inhibitory effects of CADY-NPs
on gene expression and the growth of MDR-A. baumannii.
Results: We found that CADY-NPs could be quickly internalized by drug-sensitive and MDR-A. baumannii
in an energy independent manner, which could be restrained by chlorpromazine (an inhibitor of
clathrin mediated endocytosis) significantly. In addition, CADY-NPs targeting acpP concentrationdependently
retarded the growth of MDR-A. baumannii, which was associated with the decreased expression
of targeted genes in A. baumannii.
Conclusion: In conclusion, our research is the first to demonstrate that CADY can deliver ASOs into
bacteria and provide a novel strategy for the treatment of MDR-A. baumannii.