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Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process.

ABSTRACT: Bacteriophages are bacterial viruses that infect the host after successful receptor recognition and adsorption to the cell surface. The irreversible adherence followed by genome material ejection into host cell cytoplasm must be preceded by the passage of diverse carbohydrate barriers such as capsule polysaccharides (CPSs), O-polysaccharide chains of lipopolysaccharide (LPS) molecules, extracellular polysaccharides (EPSs) forming biofilm matrix, and peptidoglycan (PG) layers. For that purpose, bacteriophages are equipped with various virion-associated carbohydrate active enzymes, termed polysaccharide depolymerases and lysins, that recognize, bind, and degrade the polysaccharide compounds. We discuss the existing diversity in structural locations, variable architectures, enzymatic specificities, and evolutionary aspects of polysaccharide depolymerases and virion-associated lysins (VALs) and illustrate how these aspects can correlate with the host spectrum. In addition, we present methods that can be used for activity determination and the application potential of these enzymes as antibacterials, antivirulence agents, and diagnostic tools.

SUBMITTER: Latka A

PROVIDER: S-EPMC5380687 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process.

Latka Agnieszka A Maciejewska Barbara B Majkowska-Skrobek Grazyna G Briers Yves Y Drulis-Kawa Zuzanna Z

Applied microbiology and biotechnology 20170323 8

Bacteriophages are bacterial viruses that infect the host after successful receptor recognition and adsorption to the cell surface. The irreversible adherence followed by genome material ejection into host cell cytoplasm must be preceded by the passage of diverse carbohydrate barriers such as capsule polysaccharides (CPSs), O-polysaccharide chains of lipopolysaccharide (LPS) molecules, extracellular polysaccharides (EPSs) forming biofilm matrix, and peptidoglycan (PG) layers. For that purpose, b ...[more]

PMID: 28337580

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Project description:BackgroundIn emergencies, language barriers may have dangerous consequences for the patients. There have been some technical approaches to overcome language barriers in medical care but not yet in the prehospital emergency care setting. The use of digital technologies in health care is expanding rapidly. Involving end users at all stages of the development process may help to ensure such technologies are usable and can be implemented.ObjectiveWe aimed to develop a digital communication tool that addresses paramedic needs in the specific circumstances of prehospital emergency care and helps paramedics to overcome language barriers when providing care to foreign-language patients.MethodsWe actively engaged paramedics and software designers in an action-oriented, participatory, iterative development process, which included field observations, workshops, background conversations, questionnaires on rescue missions, studying the literature, and preliminary testing in the field.ResultsWith input from paramedics, we created an app with 600 fixed phrases supporting 18 languages. The app includes medical history-taking questions, phrases asking for consent, and phrases providing specific additional information. Children as patients, as well as their carers and other third parties, can be addressed with appropriate wording. All phrases can be played back audibly or displayed as text. The comprehensive content is grouped into categories and adapted to diverse scenarios, which makes the tool rapidly usable. The app includes a function to document patient responses and the conversation history. For evaluation in a clinical study, the app is run on a smartphone with extra speakers to be of use in noisy environments. The use of prototypes proved valuable to verify that the content, structure, and functions discussed in theory were of value and genuinely needed in practice and that the various device control elements were intuitive.ConclusionsThe nature of the paramedic work environment places specific demands on the communication options used and need for such devices. The active involvement of paramedics in the development process allowed us to understand and subsequently consider their experience-based knowledge. Software designers could understand the paramedics' work environment and consider respective needs in the menu navigation and design principles of the app. We argue that the development of any medical software product should actively involve both end users and developers in all phases of the development process. Providing the users with the opportunity to influence technology development ensures that the result is closer to their needs, which can be seen as crucial for successful implementation and sustainable use.Trial registrationGerman Clinical Trials Register DRKS00016719; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016719.International registered report identifier (irrid)RR2-10.1186/s12913-020-05098-5.

Project description:BACKGROUND: Human cytomegalovirus (HCMV) is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE) gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF) UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1) genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. RESULTS: The UL82 homolog encoded by simian cytomegalovirus (SCMV), strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All UL82 homologs stimulated the early release of ATRX from nuclear domain 10. CONCLUSION: All of the UL82 homolog proteins analysed activated gene expression, but surprising differences in other aspects of their properties were revealed. The results provide new information on early events in infection with cytomegaloviruses.

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Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process.

Publications

Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process.

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