@article{8753544,
  abstract     = {{The rising antimicrobial resistance is particularly alarming for Acinetobacter baumannii, calling for the discovery and evaluation of alternatives to treat A. baumannii infections. Some bacteriophages produce a structural protein that depolymerizes capsular exopolysaccharide. Such purified depolymerases are considered as novel antivirulence compounds. We identified and characterized a depolymerase (DpoMK34) from Acinetobacter phage vB_AbaP_PMK34 active against the clinical isolate A. baumannii MK34. In silico analysis reveals a modular protein displaying a conserved N-terminal domain for anchoring to the phage tail, and variable central and C-terminal domains for enzymatic activity and specificity. AlphaFold-Multimer predicts a trimeric protein adopting an elongated structure due to a long alpha-helix, an enzymatic beta-helix domain and a hypervariable 4 amino acid hotspot in the most ultimate loop of the C-terminal domain. In contrast to the tail fiber of phage T3, this hypervariable hotspot appears unrelated with the primary receptor. The functional characterization of DpoMK34 revealed a mesophilic enzyme active up to 50 degrees C across a wide pH range (4 to 11) and specific for the capsule of A. baumannii MK34. Enzymatic degradation of the A. baumannii MK34 capsule causes a significant drop in phage adsorption from 95% to 9% after 5 min. Although lacking intrinsic antibacterial activity, DpoMK34 renders A. baumannii MK34 fully susceptible to serum killing in a serum concentration dependent manner. Unlike phage PMK34, DpoMK34 does not easily select for resistant mutants either against PMK34 or itself. In sum, DpoMK34 is a potential antivirulence compound that can be included in a depolymerase cocktail to control difficult to treat A. baumannii infections.}},
  articleno    = {{677}},
  author       = {{Abdelkader, Karim Abdelkader Soufi and Gutierrez Fernandez, Diana and Łątka, Agnieszka and Boeckaerts, Dimitri and Drulis-Kawa, Zuzanna and Criel, Bjorn and Gerstmans, Hans and Safaan, Amal and Khairalla, Ahmed S. and Gaber, Yasser and Dishisha, Tarek and Briers, Yves}},
  issn         = {{2079-6382}},
  journal      = {{ANTIBIOTICS-BASEL}},
  keywords     = {{Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology,Toxicology and Pharmaceutics,Biochemistry,Microbiology,capsule,depolymerase,phage,Acinetobacter baumannii,tailspike,antivirulence,HOST-RANGE,BACTERIOPHAGE,RESISTANCE,PROTEIN,ENZYMES}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{20}},
  title        = {{The specific capsule depolymerase of phage PMK34 sensitizes Acinetobacter baumannii to serum killing}},
  url          = {{http://doi.org/10.3390/antibiotics11050677}},
  volume       = {{11}},
  year         = {{2022}},
}

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