Phage φAB6-Borne Depolymerase Combats Acinetobacter baumannii Biofilm Formation and Infection

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.

Bacterial Biofilm Destruction: A Focused Review On The Recent Use of Phage-Based Strategies With Other Antibiofilm Agents

“…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 biofilms to medical device surfaces. 82 In another study, recombinant Dep42, a putative tail fiber protein with depolymerase activity from bacteriophage SH-KP152226, showed specific enzymatic activities in the depolymerization of the K47 capsule of K. pneumoniae and significantly inhibited biofilm formation and/or degrade formed biofilms. The study also showed that Dep42 could enhance polymyxin activity against K. pneumoniae biofilms when used in combination with antibiotics, suggesting that combination of identified novel depolymerases encoded by the phages with antibiotics may represent a promising strategy to combat infections caused by MDR and biofilm-forming bacteria.…”

Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter Baumannii

“…Overall, the depolymerase treatment were unable to completely inhibit or remove biofiolms and the number of viable bacterial counts in the biofilms were similar to the untreated controls [18][19][20]25], with a few exceptions [24,29]. These suggested that using depolymerases as a stand-alone treatment might not be sufficient in controlling infections associated with biofilms.…”

“…As CPS and EPS (a major component of the biofilms) are the substrates of phage encoded depolymerases, the application of recombinant depolymerases has received compelling interest as novel antivirulence agents to control multidrug-resistant infections [13,14]. A few depolymerases encoded by A. baumannii phage have been identified in recent years with demonstrated in vivo efficacy [28,29,32,45,46]. However, the synergistic effects of the combination of depolymerases and the SOC antibiotics in controlling infections caused by A. baumannii have never been attempted.…”

“…In addition, depolymerases also present high specificity toward a narrow range of target polysaccharides (specific capsular type of the bacteria). In some cases, depolymerases might only be active against a subset of bacteria of their parent phage which are already specific to a small set of bacteria strains [18,29,36]. Such narrow host spectrum would greatly limit the wider therapeutic application of depolymerases.…”

“…Currently, a few A. baumannii depolymerases have been identified [20,[28][29][30][31][32]. Whether they would work synergistically with antibiotics in controlling biofilm-associated infections, like those observed for K. pneumonia, remains questionable.…”