Abstract
Biofilm formation is one of the main causes of increased antibiotic resistance in Acinetobacter baumannii infections. Bacteriophages and their derivatives, such as tail proteins with depolymerase activity, have shown considerable potential as antibacterial or antivirulence agents against bacterial infections. Here, we gained insights into the activity of a capsular polysaccharide (CPS) depolymerase, derived from the tailspike protein (TSP) of φAB6 phage, to degrade A. baumannii biofilm in vitro. Recombinant TSP showed enzymatic activity and was able to significantly inhibit biofilm formation and degrade formed biofilms; as low as 0.78 ng, the inhibition zone can still be formed on the bacterial lawn. Additionally, TSP inhibited the colonization of A. baumannii on the surface of Foley catheter sections, indicating that it can be used to prevent the adhesion of A. baumannii to medical device surfaces. Transmission and scanning electron microscopy demonstrated membrane leakage of bacterial cells treated with TSP, resulting in cell death. The therapeutic effect of TSP in zebrafish was also evaluated and the results showed that the survival rate was significantly improved (80%) compared with that of the untreated control group (10%). Altogether, we show that TSP derived from φAB6 is expected to become a new antibiotic against multi-drug resistant A. baumannii and a biocontrol agent that prevents the formation of biofilms on medical devices.
Highlights
Biofilm formation is one of the main causes of increased antibiotic resistance in Acinetobacter baumannii infections
The results showed that the recombinant tailspike protein (TSP) could generate a translucent spot resembling a halo and the depolymerase activity was dose-dependent, even as low as 0.78 ng (Figure 1B)
Since TSP is the tailspike protein of phage φAB6 and a phage exhibits host specificity, the enzyme possessed host specificity
Summary
Biofilm formation is one of the main causes of increased antibiotic resistance in Acinetobacter baumannii infections. Bacteriophages and their derivatives, such as tail proteins with depolymerase activity, have shown considerable potential as antibacterial or antivirulence agents against bacterial infections. We show that TSP derived from φAB6 is expected to become a new antibiotic against multi-drug resistant A. baumannii and a biocontrol agent that prevents the formation of biofilms on medical devices. Several studies have demonstrated that biofilm formation facilitates the survival and persistence of A. baumannii on abiotic hospital surfaces, resulting in tenacious and recurring nosocomial infections and is a major cause of antibiotic resistance and strong survival adaptability [4,5,6,7]. Novel methodologies are needed to control this evolving pathogen
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