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The Specific Capsule Depolymerase of Phage PMK34 Sensitizes Acinetobacter baumannii to Serum Killing.


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 α-helix, an enzymatic β-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 °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.

SUBMITTER: Abdelkader K 

PROVIDER: S-EPMC9137491 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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The Specific Capsule Depolymerase of Phage PMK34 Sensitizes <i>Acinetobacter baumannii</i> to Serum Killing.

Abdelkader Karim K   Gutiérrez Diana D   Latka Agnieszka A   Boeckaerts Dimitri D   Drulis-Kawa Zuzanna Z   Criel Bjorn B   Gerstmans Hans H   Safaan Amal A   Khairalla Ahmed S AS   Gaber Yasser Y   Dishisha Tarek T   Briers Yves Y  

Antibiotics (Basel, Switzerland) 20220517 5


The rising antimicrobial resistance is particularly alarming for <i>Acinetobacter baumannii</i>, calling for the discovery and evaluation of alternatives to treat <i>A. baumannii</i> 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  ...[more]

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