Acinetobacter Baumannii Phages: Past, Present and Future

Viruses, Год журнала: 2023, Номер 15(3), С. 673 - 673

Опубликована: Март 3, 2023

Acinetobacter baumannii (A. baumannii) is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With increase drug-resistant A. infections, it urgent to find some new treatment strategies, such as phage therapy. In this paper, we described different drug resistances basic properties phages, analyzed interaction between phages their hosts, focused on therapies. Finally, discussed chance challenge This paper aims provide more comprehensive understanding theoretical support for application phages.

Язык: Английский

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Potential of phage depolymerase for the treatment of bacterial biofilms

Virulence, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 24, 2023

Resistance of bacteria to antibiotics is a major concern in medicine and veterinary science. The bacterial biofilm structures not only prevent the penetration drugs into cells within biofilm's interior but also aid evasion host immune system. Hence, there an urgent need develop novel therapeutic approaches against biofilms. One potential strategy counter biofilms use phage depolymerases that degrade matrix structure enable access cells. This review mainly discusses methods by which enhance efficacy human system applications some depolymerases, such as single depolymerase application, combined therapy with antibiotics, cocktails, for treating summarizes relationship between antibiotic resistance.

Язык: Английский

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Genome-wide phage susceptibility analysis in Acinetobacter baumannii reveals capsule modulation strategies that determine phage infectivity

PLoS Pathogens, Год журнала: 2023, Номер 19(6), С. e1010928 - e1010928

Опубликована: Июнь 8, 2023

Phage have gained renewed interest as an adjunctive treatment for life-threatening infections with the resistant nosocomial pathogen Acinetobacter baumannii . Our understanding of how A defends against phage remains limited, although this information could lead to improved antimicrobial therapies. To address problem, we identified genome-wide determinants susceptibility in using Tn-seq. These studies focused on lytic Loki, which targets by unknown mechanisms. We 41 candidate loci that increase Loki when disrupted, and 10 decrease susceptibility. Combined spontaneous resistance mapping, our results support model uses K3 capsule essential receptor, modulation provides strategies control vulnerability phage. key center is transcriptional regulation synthesis virulence global regulator BfmRS. Mutations hyperactivating BfmRS simultaneously levels, adsorption, replication, host killing, while BfmRS-inactivating mutations opposite effect, reducing blocking infection. novel BfmRS-activating mutations, including knockouts a T2 RNase protein disulfide formation enzyme DsbA, hypersensitize bacteria challenge. further found mutation glycosyltransferase known alter structure bacterial can also cause complete resistance. Finally, additional factors lipooligosaccharide Lon protease act independently interfere This work demonstrates regulatory structural capsule, virulence, major determinant

Язык: Английский

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Structural diversity among Acinetobacter baumannii K-antigens and its implication in the in silico serotyping

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Июнь 21, 2023

Acinetobacter baumannii is an emerging opportunistic pathogen. It exhibits multi-, extreme-, and pan-drug resistance against several classes of antibiotics. Capsular polysaccharide (CPS or K-antigen) one the major virulence factors which aids A. in evading host immune system. K-antigens exploit Wzx/Wzy-dependent pathway that involves 13 different proteins for its assembly transport onto outer membrane. A total 64 (out 237 K-locus(KL) types) known K-antigen sugar repeating structures are discussed here classified into seven groups based on their initial sugars, QuiNAc4NAc, GalNAc, GlcNAc, Gal, QuiNAc/FucNAc, FucNAc, GlcNAc along with Leg5Ac7Ac/Leg5Ac7R. Thus, corresponding initializing glycosyltransferases (ItrA1, ItrA2, ItrA3, ItrA4, ItrB1, ItrB3, ItrA3 ItrB2) exhibit serotype specificity. The modeled 3D-structural repository can be accessed at https://project.iith.ac.in/ABSD/k_antigen.html . topology further reveals presence 2-6 0-4 monomers main side chains, respectively. negatively (predominant) neutrally charged observed Such diversity composition provides K-typing specificity ( viz ., 18–69% terms reliability) Wza, Wzb, Wzc, Wzx, Wzy involved pathway. Interestingly, degree uniqueness these among K-types estimated to 76.79%, considering reference sequences. This article summarizes structural creation a digital systematic analysis transportation marker proteins.

Язык: Английский

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Lytic Capsule-Specific Acinetobacter Bacteriophages Encoding Polysaccharide-Degrading Enzymes

Viruses, Год журнала: 2024, Номер 16(5), С. 771 - 771

Опубликована: Май 13, 2024

The genus Acinetobacter comprises both environmental and clinically relevant species associated with hospital-acquired infections. Among them, baumannii is a critical priority bacterial pathogen, for which the research development of new strategies antimicrobial treatment are urgently needed. spp. produce variety structurally diverse capsular polysaccharides (CPSs), surround cells thick protective layer. These surface structures primary receptors capsule-specific bacteriophages, that is, phages carrying tailspikes CPS-depolymerizing/modifying activities. Phage tailspike proteins (TSPs) exhibit hydrolase, lyase, or esterase activities toward corresponding CPSs certain structure. In this study, data on all lytic infecting genomes deposited in NCBI GenBank database by January 2024 were summarized. 149 identified TSPs encoded 143 phages, specificity (K specificity) 46 has been experimentally determined predicted previously. 63 CPSs, produced various K types, was study using bioinformatic analysis. A comprehensive phylogenetic analysis confirmed prediction revealed possibility genetic exchange gene regions to CPS-recognizing/degrading parts different between morphologically taxonomically distant groups phages.

Язык: Английский

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Friunavirus Phage-Encoded Depolymerases Specific to Different Capsular Types of Acinetobacter baumannii

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(10), С. 9100 - 9100

Опубликована: Май 22, 2023

Acinetobacter baumannii is a critical priority nosocomial pathogen that produces variety of capsular polysaccharides (CPSs), the primary receptors for specific depolymerase-carrying phages. In this study, tailspike depolymerases (TSDs) encoded in genomes six novel Friunaviruses, APK09, APK14, APK16, APK86, APK127v, APK128, and one previously described Friunavirus phage, APK37.1, were characterized. For all TSDs, mechanism cleavage corresponding A. (CPSs) was established. The structures oligosaccharide fragments derived from K9, K14, K16, K37/K3-v1, K86, K127, K128 CPSs degradation by recombinant have been determined. crystal three studied TSDs obtained. A significant reduction mortality Galleria mellonella larvae infected with K9 type shown example TSD APK09_gp48. data obtained will provide better understanding interaction phage-bacterial host systems contribute to formation principles rational usage lytic phages phage-derived enzymes as antibacterial agents.

Язык: Английский

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Host range expansion of Acinetobacter phage vB_Ab4_Hep4 driven by a spontaneous tail tubular mutation

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Фев. 16, 2024

Bacteriophages (phages) represent promising alternative treatments against multidrug-resistant Acinetobacter baumannii (MDRAB) infections. The application of phages as antibacterial agents is limited by their generally narrow host ranges, so changing or expanding the ranges beneficial for phage therapy. Multiple studies have identified that tail fiber protein mediates recognition and binding to receptor in infection. However, tubular-dependent specificity has not been studied well. In this study, we isolated characterized a novel lytic phage, vB_Ab4_Hep4, specifically infecting MDRAB strains. Meanwhile, spontaneous mutant vB_Ab4_Hep4-M, which revealed an expanded range compared wild-type phage. A single mutation G C was detected gene encoding tubular B thus resulted aspartate histidine change. We further demonstrated expansion driven guanine cytosine using expressed B. Moreover, established bacterial capsule Abp4 Abp4-M identifying genes phage-resistant conclusion, our study provided detailed description vB_Ab4_Hep4 A. phages, may provide new insights into extending gene-modifying proteins.

Язык: Английский

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Characterization of the carbapenem-resistant Acinetobacter baumannii clinical reference isolate BAL062 (CC2:KL58:OCL1): resistance properties and capsular polysaccharide structure

mSystems, Год журнала: 2024, Номер unknown

Опубликована: Сен. 10, 2024

ABSTRACT The carbapenem-resistant Acinetobacter baumannii isolate BAL062 is a clinical reference used in several recent experimental studies. It from ventilator-associated pneumonia (VAP) patient an intensive care unit at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam 2009. Here, was found to belong B sub-lineage of global clone 2 (GC2) isolates previously reported outbreak (2008 and 2012) VAP A. HTD. While related were extensively antibiotic-resistant carry GC2-associated genomic resistance islands, AbGRI1, AbGRI2, AbGRI3, has lost AbGRI3 three aminoglycoside genes, armA, aacA4, aphA1 , leading amikacin, tobramycin kanamycin susceptibility. location Tn 2008 VAR chromosome this also corrected. Like many isolates, carries KL58 gene cluster capsular polysaccharide (CPS) synthesis locus annotation key provided. As information about K type important development novel CPS-targeting therapies, K58-type CPS structure established using NMR spectroscopy. most closely K2 K93, sharing similar configurations linkages between units, contains rare higher monosaccharide, 5,7-diacetamido-3,5,7,9-tetradeoxy- d - glycero l manno -non-2-ulosonic acid (5,7-di- N -acetyl-8-epipseudaminic acid; 8ePse5Ac7Ac), 8-epimer Pse5Ac7Ac -acetylpseudaminic acid). Inspection publicly available genomes revealed wide distribution geographically diverse belonging sequence types that recovered over two decades clinical, animal, environmental sources. IMPORTANCE Many published studies aimed developing clearer understanding pathogenicity strains currently causing treatment failure due extensive antibiotic are undertaken historic, laboratory-adapted isolates. However, it ideal if not imperative such characterized here belongs dominant GC2 resistant infections been various correlation profiles data identifying genes knockout complementation analyses, we have mapped find candidates. Novel as bacteriophage or monoclonal antibody under investigation alternatives adjuncts combat difficult-to-treat CRAb often exhibit specificity specific structural epitopes (CPS), outer-most layer. solved other consistent naming identification interpretation studies, correlated automatic annotations standard names.

Язык: Английский

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The Acinetobacter baumannii K70 and K9 capsular polysaccharides consist of related K-units linked by the same Wzy polymerase and cleaved by the same phage depolymerases

Microbiology Spectrum, Год журнала: 2023, Номер 11(6)

Опубликована: Ноя. 17, 2023

Bacteriophage show promise for the treatment of Acinetobacter baumannii infections that resist all therapeutically suitable antibiotics. Many tail-spike depolymerases encoded by phage are able to degrade A. capsular polysaccharide (CPS) exhibit specificity linkage present between K-units make up CPS polymers. This is formed a specific Wzy polymerase, and ability predict this using sequence-based methods identify at K locus could assist with selection therapy. However, little known about polymerase enzymes. Here, we describe can accommodate two different but similar sugars as one residues it links cleave both types bond forms.

Язык: Английский

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The Acinetobacter baumannii K239 capsular polysaccharide includes heptasaccharide units that are structurally related to K86 but joined by different linkages formed by different Wzy polymerases

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 262, С. 130045 - 130045

Опубликована: Фев. 7, 2024

The K239 type capsular polysaccharide (CPS) isolated from Acinetobacter baumannii isolate MAR19-4435 was studied by sugar analysis, one- and two-dimensional 1H 13C NMR spectroscopy. consists of branched heptasaccharide repeats (K-units) comprised five residues l-rhamnose (l-Rhap), one residue each d-glucuronic acid (d-GlcpA) N-acetyl-d-glucosamine (d-GlcpNAc). structure is closely related to that the A. K86 CPS type, though two differ in 2,3-substitution patterns on l-Rhap involved linkage between K-units polymer. This structural difference attributed presence a gtr221 glycosyltransferase gene wzyKL239 polymerase KL239 replaces gtr80 wzyKL86 genes KL86 biosynthesis cluster. Comparison structures established role novel WzyKL239 encoded forms β-D-GlcpNAc-(1 → 2)-L-Rhap units. found be non-susceptible infection APK86 bacteriophage, which encodes depolymerase specifically cleaves CPS, indicating influences susceptibility this bacteriophage activity.

Язык: Английский

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