A chionodracine-derived peptide, KHS-Cnd, as an anti-virulence agent against multidrug-resistant Acinetobacter baumannii clinical strains
Author(s)
Date Issued
2025
Type
article
Volume
15
Start Page
1
End Page
11
Abstract
About 71% of healthcare-associated infections are due to antibiotic-resistant
bacteria, such as carbapenem-resistant A. baumannii, classified by World Health
Organization into a critical priority group of pathogens. The antimicrobial
resistance profile of A. baumannii relies on its ability to produce several
virulence factors, including biofilm formation. Its ability to adhere and persist
on surfaces as biofilm has contributed to its pathogenicity and drug resistance. In
this study, the ability of an antimicrobial peptide (a chionodracine-derived
peptide named KHS-Cnd) to inhibit or reduce biofilm formation was
investigated as an example of a potential strategy to counteract infections
caused by biofilm-forming pathogens. To this aim, the antimicrobial profiles
were first analyzed in selected A. baumannii strains, two reference and six clinical
strains, all biofilm-forming with different capability, regardless of whether they
are drug resistant or sensitive. Successively, we investigated the bactericidal
activity of the peptide that showed MIC values ranging from 5 to 10 μM and a
significative antibiofilm activity on all tested strains at sub-inhibitory
concentrations. In fact, KHS-Cnd can hinder biofilm A. baumannii strains
formation with an inhibition percentage ranging between 65% and 10%. Also a
statistically significant reduction of mature biofilm ranging from 20% to 50% was
observed in four out of eight tested A. baumannii strains. KHS-Cnd impacts
various stages of biofilm formation, including the inhibition of surface-associated
and twitching motilities depending on the different strain. In particular, our results
showed that only two strains possessed surface-associated motility that was
strongly impaired by KHS-Cnd treatment; three clinical strains, instead, showed
twitching motility, whose inhibition for two of them was evident after 24 h of
incubation with peptide. Moreover, the invasion of pulmonary cells by A.
baumannii was significantly impaired with a reduction of about 32% after
treatment with 1.25 μM KHS-Cnd. Finally, when the peptide was used together
with ceftazidime/avibactam against resistant A. baumannii strains, it was able to
reduce the minimal inhibitory concentration of antibiotics needed to inhibit the
microorganism growth.