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The specific capsule depolymerase of phage PMK34 sensitizes Acinetobacter baumannii to serum killing

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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.
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

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MLA
Abdelkader, Karim Abdelkader Soufi, et al. “The Specific Capsule Depolymerase of Phage PMK34 Sensitizes Acinetobacter Baumannii to Serum Killing.” ANTIBIOTICS-BASEL, vol. 11, no. 5, 2022, doi:10.3390/antibiotics11050677.
APA
Abdelkader, K. A. S., Gutierrez Fernandez, D., Łątka, A., Boeckaerts, D., Drulis-Kawa, Z., Criel, B., … Briers, Y. (2022). The specific capsule depolymerase of phage PMK34 sensitizes Acinetobacter baumannii to serum killing. ANTIBIOTICS-BASEL, 11(5). https://doi.org/10.3390/antibiotics11050677
Chicago author-date
Abdelkader, Karim Abdelkader Soufi, Diana Gutierrez Fernandez, Agnieszka Łątka, Dimitri Boeckaerts, Zuzanna Drulis-Kawa, Bjorn Criel, Hans Gerstmans, et al. 2022. “The Specific Capsule Depolymerase of Phage PMK34 Sensitizes Acinetobacter Baumannii to Serum Killing.” ANTIBIOTICS-BASEL 11 (5). https://doi.org/10.3390/antibiotics11050677.
Chicago author-date (all authors)
Abdelkader, Karim Abdelkader Soufi, Diana Gutierrez Fernandez, Agnieszka Łątka, Dimitri Boeckaerts, Zuzanna Drulis-Kawa, Bjorn Criel, Hans Gerstmans, Amal Safaan, Ahmed S. Khairalla, Yasser Gaber, Tarek Dishisha, and Yves Briers. 2022. “The Specific Capsule Depolymerase of Phage PMK34 Sensitizes Acinetobacter Baumannii to Serum Killing.” ANTIBIOTICS-BASEL 11 (5). doi:10.3390/antibiotics11050677.
Vancouver
1.
Abdelkader KAS, Gutierrez Fernandez D, Łątka A, Boeckaerts D, Drulis-Kawa Z, Criel B, et al. The specific capsule depolymerase of phage PMK34 sensitizes Acinetobacter baumannii to serum killing. ANTIBIOTICS-BASEL. 2022;11(5).
IEEE
[1]
K. A. S. Abdelkader et al., “The specific capsule depolymerase of phage PMK34 sensitizes Acinetobacter baumannii to serum killing,” ANTIBIOTICS-BASEL, vol. 11, no. 5, 2022.
@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://dx.doi.org/10.3390/antibiotics11050677}},
  volume       = {{11}},
  year         = {{2022}},
}

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