Capsule-Targeting Depolymerases Derived from Acinetobacter baumannii Prophage Regions

Drobiazko, Alena; Kasimova, Аnastasia A.; Evseev, Peter; Shneider, Mikhail M.; Klimuk, Evgeny; Shashkov, Alexander S.; Dmitrenok, Andrey S.; Chizhov, Alexander O.; Slukin, Pavel V.; Skryabin, Yury P.; Volozhantsev, Nikolay V.; Miroshnikov, Konstantin A.; Knirel, Yuriy A.; Popova, Anastasiya V.

doi:10.3390/ijms23094971

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…These phages include AP22 (gp54), APK32 (gp46), APK48 (gp43), P1 (gp43), B9 (gp69), and TaPaz (gp79) (Oliveira et al, 2017 , 2018 ; Knirel et al, 2020 ; Popova et al, 2020a ; Shchurova et al, 2021 ). Furthermore, halo formation was detailed in the following phages but the protein responsible was not confirmed: AbTj (gp53) and WCHABP1 (gp5) (Zhou et al, 2018 ; Xu et al, 2020 ; Drobiazko et al, 2022 ). All the eight abovementioned proteins were modeled as homotrimers with AlphaFold Multimer and showed narrow midsections and larger globular regions ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

“…Many groups have investigated phage-encoded depolymerases and endolysins for therapeutic use (Liu et al, 2019a ; Kim et al, 2020 ; Khan et al, 2021 ; Abdelkader et al, 2022 ; Chen et al, 2022 ; Drobiazko et al, 2022 ). The potential therapeutic benefit of depolymerases is the removal of the capsule layer from the infecting bacterium, which exposes the bacterium to the innate immune system and thus activates serum killing.…”

Section: Introductionmentioning

confidence: 99%

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Functional domains of Acinetobacter bacteriophage tail fibers

Peters,

Gaudreault,

Chen

2024

Front. Microbiol.

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A rapid increase in antimicrobial resistant bacterial infections around the world is causing a global health crisis. The Gram-negative bacterium Acinetobacter baumannii is categorized as a Priority 1 pathogen for research and development of new antimicrobials by the World Health Organization due to its numerous intrinsic antibiotic resistance mechanisms and ability to quickly acquire new resistance determinants. Specialized phage enzymes, called depolymerases, degrade the bacterial capsule polysaccharide layer and show therapeutic potential by sensitizing the bacterium to phages, select antibiotics, and serum killing. The functional domains responsible for the capsule degradation activity are often found in the tail fibers of select A. baumannii phages. To further explore the functional domains associated with depolymerase activity, tail-associated proteins of 71 sequenced and fully characterized phages were identified from published literature and analyzed for functional domains using InterProScan. Multisequence alignments and phylogenetic analyses were conducted on the domain groups and assessed in the context of noted halo formation or depolymerase characterization. Proteins derived from phages noted to have halo formation or a functional depolymerase, but no functional domain hits, were modeled with AlphaFold2 Multimer, and compared to other protein models using the DALI server. The domains associated with depolymerase function were pectin lyase-like (SSF51126), tailspike binding (cd20481), (Trans)glycosidases (SSF51445), and potentially SGNH hydrolases. These findings expand our knowledge on phage depolymerases, enabling researchers to better exploit these enzymes for therapeutic use in combating the antimicrobial resistance crisis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional domains of Acinetobacter bacteriophage tail fibers

Peters,

Gaudreault,

Chen

2024

Front. Microbiol.

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“…Putative depolymerase domain-containing proteins assigned to Cluster 4 and Cluster 5 demonstrated a structural architecture typical of tail fibre (spike) proteins [ 72 , 73 ], including those found in prophage regions [ 74 ]. These proteins contained a parallel β-structured pyramidal central part, formed upon trimerisation ( Supplementary Figure S10a ).…”

Section: Resultsmentioning

confidence: 99%

Prophage-Derived Regions in Curtobacterium Genomes: Good Things, Small Packages

Evseev

Lukianova

Tarakanov

et al. 2023

IJMS

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Curtobacterium is a genus of Gram-positive bacteria within the order Actinomycetales. Some Curtobacterium species (C. flaccumfaciens, C. plantarum) are harmful pathogens of agricultural crops such as soybean, dry beans, peas, sugar beet and beetroot, which occur throughout the world. Bacteriophages (bacterial viruses) are considered to be potential curative agents to control the spread of harmful bacteria. Temperate bacteriophages integrate their genomes into bacterial chromosomes (prophages), sometimes substantially influencing bacterial lifestyle and pathogenicity. About 200 publicly available genomes of Curtobacterium species, including environmental metagenomic sequences, were inspected for the presence of sequences of possible prophage origin using bioinformatic methods. The comparison of the search results with several ubiquitous bacterial groups showed the relatively low level of the presence of prophage traces in Curtobacterium genomes. Genomic and phylogenetic analyses were undertaken for the evaluation of the evolutionary and taxonomic positioning of predicted prophages. The analyses indicated the relatedness of Curtobacterium prophage-derived sequences with temperate actinophages of siphoviral morphology. In most cases, the predicted prophages can represent novel phage taxa not described previously. One of the predicted temperate phages was induced from the Curtobacterium genome. Bioinformatic analysis of the modelled proteins encoded in prophage-derived regions led to the discovery of some 100 putative glycopolymer-degrading enzymes that contained enzymatic domains with predicted cell-wall- and cell-envelope-degrading activity; these included glycosidases and peptidases. These proteins can be considered for the experimental design of new antibacterials against Curtobacterium phytopathogens.

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“…This concept is supported by the fact that purified recombinant, phage-derived tail spike proteins are able to remove the capsules or O antigens from the cell surface (see [70] for review). The enzymatic decapsulation of Klebsiella, Acinetobacter and some other bacteria by phage-derived proteins is demonstrably effective in treating experimental infections [69][70][71]75,76]. This is because removing the capsule makes the cells more vulnerable for the immune system of the macroorganism.…”

Section: Podoviruses: Cut or Pull?mentioning

confidence: 99%

Bacterial Virus Forcing of Bacterial O-Antigen Shields: Lessons from Coliphages

Letarov

2023

IJMS

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In most Gram-negative bacteria, outer membrane (OM) lipopolysaccharide (LPS) molecules carry long polysaccharide chains known as the O antigens or O polysaccharides (OPS). The OPS structure varies highly from strain to strain, with more than 188 O serotypes described in E. coli. Although many bacteriophages recognize OPS as their primary receptors, these molecules can also screen OM proteins and other OM surface receptors from direct interaction with phage receptor-binding proteins (RBP). In this review, I analyze the body of evidence indicating that most of the E. coli OPS types robustly shield cells completely, preventing phage access to the OM surface. This shield not only blocks virulent phages but also restricts the acquisition of prophages. The available data suggest that OPS-mediated OM shielding is not merely one of many mechanisms of bacterial resistance to phages. Rather, it is an omnipresent factor significantly affecting the ecology, phage–host co-evolution and other related processes in E. coli and probably in many other species of Gram-negative bacteria. The phages, in turn, evolved multiple mechanisms to break through the OPS layer. These mechanisms rely on the phage RBPs recognizing the OPS or on using alternative receptors exposed above the OPS layer. The data allow one to forward the interpretation that, regardless of the type of receptors used, primary receptor recognition is always followed by the generation of a mechanical force driving the phage tail through the OPS layer. This force may be created by molecular motors of enzymatically active tail spikes or by virion structural re-arrangements at the moment of infection.

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Capsule-Targeting Depolymerases Derived from Acinetobacter baumannii Prophage Regions

Cited by 11 publications

References 41 publications

Functional domains of Acinetobacter bacteriophage tail fibers

Functional domains of Acinetobacter bacteriophage tail fibers

Prophage-Derived Regions in Curtobacterium Genomes: Good Things, Small Packages

Bacterial Virus Forcing of Bacterial O-Antigen Shields: Lessons from Coliphages

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