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  1. Article: Reporter-Phage-Based Detection and Antibiotic Susceptibility Testing of Yersinia pestis for a Rapid Plague Outbreak Response

    Moses, Sarit / Aftalion, Moshe / Mamroud, Emanuelle / Rotem, Shahar / Steinberger-Levy, Ida

    Microorganisms. 2021 June 11, v. 9, no. 6

    2021  

    Abstract: Pneumonic plague is a lethal infectious disease caused by Yersinia pestis, a Tier-1 biothreat agent. Antibiotic treatment can save infected patients; however, therapy should begin within 24 h of symptom onset. As some Y. pestis strains showed an ... ...

    Abstract Pneumonic plague is a lethal infectious disease caused by Yersinia pestis, a Tier-1 biothreat agent. Antibiotic treatment can save infected patients; however, therapy should begin within 24 h of symptom onset. As some Y. pestis strains showed an antibiotic resistance phenotype, an antibiotic susceptibility test (AST) must be performed. Performing the Clinical and Laboratory Standards Institute (CLSI)-recommended standard process, which includes bacterial isolation, enumeration and microdilution testing, lasts several days. Thus, rapid AST must be developed. As previously published, the Y. pestis-specific reporter phage ϕA1122::luxAB can serve for rapid identification and AST (ID-AST). Herein, we demonstrate the ability to use ϕA1122::luxAB to determine minimal inhibitory concentration (MIC) values and antibiotic susceptibility categories for various Y. pestis therapeutic antibiotics. We confirmed the assay by testing several nonvirulent Y. pestis isolates with reduced susceptibility to doxycycline or ciprofloxacin. Moreover, the assay can be performed directly on positive human blood cultures. Furthermore, as Y. pestis may naturally or deliberately be spread in the environment, we demonstrate the compatibility of this direct method for this scenario. This direct phage-based ID-AST shortens the time needed for standard AST to less than a day, enabling rapid and correct treatment, which may also prevent the spread of the disease.
    Keywords Yersinia pestis ; antibiotic resistance ; bacteriophages ; blood ; ciprofloxacin ; disease transmission ; doxycycline ; humans ; minimum inhibitory concentration ; phenotype ; plague ; therapeutics
    Language English
    Dates of publication 2021-0611
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9061278
    Database NAL-Catalogue (AGRICOLA)

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  2. Article: Beating the Bio-Terror Threat with Rapid Antimicrobial Susceptibility Testing

    Rotem, Shahar / Steinberger-Levy, Ida / Israeli, Ofir / Zahavy, Eran / Aloni-Grinstein, Ronit

    Microorganisms. 2021 July 19, v. 9, no. 7

    2021  

    Abstract: A bioterror event using an infectious bacterium may lead to catastrophic outcomes involving morbidity and mortality as well as social and psychological stress. Moreover, a bioterror event using an antibiotic resistance engineered bacterial agent may ... ...

    Abstract A bioterror event using an infectious bacterium may lead to catastrophic outcomes involving morbidity and mortality as well as social and psychological stress. Moreover, a bioterror event using an antibiotic resistance engineered bacterial agent may raise additional concerns. Thus, preparedness is essential to preclude and control the dissemination of the bacterial agent as well as to appropriately and promptly treat potentially exposed individuals or patients. Rates of morbidity, death, and social anxiety can be drastically reduced if the rapid delivery of antimicrobial agents for post-exposure prophylaxis and treatment is initiated as soon as possible. Availability of rapid antibiotic susceptibility tests that may provide key recommendations to targeted antibiotic treatment is mandatory, yet, such tests are only at the development stage. In this review, we describe the recently published rapid antibiotic susceptibility tests implemented on bioterror bacterial agents and discuss their assimilation in clinical and environmental samples.
    Keywords antibiotic resistance ; antibiotics ; anxiety ; bacteria ; death ; disease prevention ; morbidity ; mortality ; psychological stress
    Language English
    Dates of publication 2021-0719
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9071535
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Reporter-Phage-Based Detection and Antibiotic Susceptibility Testing of

    Moses, Sarit / Aftalion, Moshe / Mamroud, Emanuelle / Rotem, Shahar / Steinberger-Levy, Ida

    Microorganisms

    2021  Volume 9, Issue 6

    Abstract: Pneumonic plague is a lethal infectious disease caused ... ...

    Abstract Pneumonic plague is a lethal infectious disease caused by
    Language English
    Publishing date 2021-06-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9061278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Beating the Bio-Terror Threat with Rapid Antimicrobial Susceptibility Testing.

    Rotem, Shahar / Steinberger-Levy, Ida / Israeli, Ofir / Zahavy, Eran / Aloni-Grinstein, Ronit

    Microorganisms

    2021  Volume 9, Issue 7

    Abstract: A bioterror event using an infectious bacterium may lead to catastrophic outcomes involving morbidity and mortality as well as social and psychological stress. Moreover, a bioterror event using an antibiotic resistance engineered bacterial agent may ... ...

    Abstract A bioterror event using an infectious bacterium may lead to catastrophic outcomes involving morbidity and mortality as well as social and psychological stress. Moreover, a bioterror event using an antibiotic resistance engineered bacterial agent may raise additional concerns. Thus, preparedness is essential to preclude and control the dissemination of the bacterial agent as well as to appropriately and promptly treat potentially exposed individuals or patients. Rates of morbidity, death, and social anxiety can be drastically reduced if the rapid delivery of antimicrobial agents for post-exposure prophylaxis and treatment is initiated as soon as possible. Availability of rapid antibiotic susceptibility tests that may provide key recommendations to targeted antibiotic treatment is mandatory, yet, such tests are only at the development stage. In this review, we describe the recently published rapid antibiotic susceptibility tests implemented on bioterror bacterial agents and discuss their assimilation in clinical and environmental samples.
    Language English
    Publishing date 2021-07-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9071535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Global transcriptomic analysis of Francisella tularensis SchuS4 differentially expressed genes in response to doxycycline or ciprofloxacin exposure.

    Zaide, Galia / Cohen-Gihon, Inbar / Shifman, Ohad / Israeli, Ofir / Aftalion, Moshe / Maoz, Sharon / Chitlaru, Theodor / Ber, Raphael / Zvi, Anat / Steinberger-Levy, Ida

    BMC genomic data

    2023  Volume 24, Issue 1, Page(s) 23

    Abstract: Objective: As part of a research aiming at presenting an alternative approach for rapid determination of antimicrobial susceptibility by quantification of changes in expression levels of specific marker genes and gene sets, cultures of the virulent ... ...

    Abstract Objective: As part of a research aiming at presenting an alternative approach for rapid determination of antimicrobial susceptibility by quantification of changes in expression levels of specific marker genes and gene sets, cultures of the virulent bacterial strain Francisella tularensis SchuS4 were grown in the presence of inhibitory/sub-inhibitory concentrations of either ciprofloxacin or doxycycline and their transcriptomic profiles were elucidated using differential expression analysis followed by functional annotation.
    Data description: RNA sequencing was performed to identify differentially expressed genes (DEGs) in response to exposure of F. tularensis SchuS4 to either ciprofloxacin or doxycycline, the antibiotics of choice for Tularemia therapy. Accordingly, RNA samples were collected 2 h post antibiotic exposure and subjected to RNA sequence analysis. Transcriptomic quantification of RNA representing duplicated samples generated highly similar gene expression data. Exposure to sub-inhibitory concentration [0.5 x MIC (minimal inhibitory concentration)] of doxycycline or ciprofloxacin modulated the expression of 237 or 8 genes, respectively, while exposure to an inhibitory concentration (1 x MIC) resulted in the modulation of 583 or 234 genes, respectively. Amongst the genes modulated upon doxycycline exposure upregulation of 31 genes encoding for translation-functions could be distinguished, as well as downregulation of 14 genes encoding for functions involved in DNA transcription and repair. Ciprofloxacin exposure impacted differently the RNA sequence profile of the pathogen, resulting in upregulation of 27 genes encoding mainly DNA replication and repair functions, transmembrane transporters and molecular chaperons. In addition, 15 downregulated genes were involved in translation processes.
    MeSH term(s) Doxycycline/pharmacology ; Francisella tularensis/genetics ; Ciprofloxacin/pharmacology ; Transcriptome/genetics ; Anti-Bacterial Agents/pharmacology ; RNA
    Chemical Substances Doxycycline (N12000U13O) ; Ciprofloxacin (5E8K9I0O4U) ; Anti-Bacterial Agents ; RNA (63231-63-0)
    Language English
    Publishing date 2023-04-19
    Publishing country England
    Document type Journal Article
    ISSN 2730-6844
    ISSN (online) 2730-6844
    DOI 10.1186/s12863-023-01125-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Characterization of

    Moses, Sarit / Vagima, Yaron / Tidhar, Avital / Aftalion, Moshe / Mamroud, Emanuelle / Rotem, Shahar / Steinberger-Levy, Ida

    Viruses

    2021  Volume 13, Issue 1

    Abstract: The global increase in multidrug-resistant (MDR) pathogenic bacteria has led to growing interest in bacteriophage ("phage") therapy. Therapeutic phages are usually selected based on their ability to infect and lyse target bacteria, using in vitro assays. ...

    Abstract The global increase in multidrug-resistant (MDR) pathogenic bacteria has led to growing interest in bacteriophage ("phage") therapy. Therapeutic phages are usually selected based on their ability to infect and lyse target bacteria, using in vitro assays. In these assays, phage infection is determined using target bacteria grown in standard commercial rich media, while evaluation of the actual therapeutic activity requires the presence of human blood. In the present work, we characterized the ability of two different
    MeSH term(s) Bacteriolysis ; Bacteriophages/physiology ; Humans ; Phage Therapy ; Plague/therapy ; Plague/virology ; Precision Medicine ; Viral Load ; Yersinia pestis/virology
    Language English
    Publishing date 2021-01-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13010089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Phage Therapy Potentiates Second-Line Antibiotic Treatment against Pneumonic Plague.

    Vagima, Yaron / Gur, David / Aftalion, Moshe / Moses, Sarit / Levy, Yinon / Makovitzki, Arik / Holtzman, Tzvi / Oren, Ziv / Segula, Yaniv / Fatelevich, Ella / Tidhar, Avital / Zauberman, Ayelet / Rotem, Shahar / Mamroud, Emanuelle / Steinberger-Levy, Ida

    Viruses

    2022  Volume 14, Issue 4

    Abstract: Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the ... ...

    Abstract Plague pandemics and outbreaks have killed millions of people during the history of humankind. The disease, caused by the bacteria
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacteriophages ; Disease Models, Animal ; Humans ; Mice ; Phage Therapy ; Plague/drug therapy ; Yersinia pestis
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2022-03-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14040688
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Evaluation of the European Committee on Antimicrobial Susceptibility Testing Guidelines for Rapid Antimicrobial Susceptibility Testing of Bacillus anthracis-, Yersinia pestis- and Francisella tularensis-Positive Blood Cultures

    Shifman, Ohad / Aminov, Tamar / Aftalion, Moshe / Gur, David / Cohen, Hila / Bar-David, Elad / Cohen, Ofer / Mamroud, Emanuelle / Levy, Haim / Aloni-Grinstein, Ronit / Steinberger-Levy, Ida / Rotem, Shahar

    Microorganisms. 2021 May 13, v. 9, no. 5

    2021  

    Abstract: Rapid determination of bacterial antibiotic susceptibility is important for proper treatment of infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recently published guidelines for rapid antimicrobial susceptibility ... ...

    Abstract Rapid determination of bacterial antibiotic susceptibility is important for proper treatment of infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recently published guidelines for rapid antimicrobial susceptibility testing (RAST) performed directly from positive blood culture vials. These guidelines, however, were only published for a limited number of common pathogenic bacteria. In this study, we evaluated the applicability of these guidelines to three Tier 1 bioterror agents (Bacillus anthracis, Yersinia pestis and Francisella tularensis) that require prompt antibiotic treatment to mitigate morbidity and mortality. We used spiked-in human blood incubated in a BACTEC™ FX40 system to determine the proper conditions for RAST using disc-diffusion and Etest assays. We found that reliable disc-diffusion inhibition diameters and Etest MIC values could be obtained in remarkably short times. Compared to the EUCAST-recommended disc-diffusion assays that will require adjusted clinical breakpoint tables, Etest-based RAST was advantageous, as the obtained MIC values were similar to the standard MIC values, enabling the use of established category breakpoint tables. Our results demonstrate the promising applicability of the EUCAST RAST for B. anthracis-, Y. pestis- or F. tularensis-positive blood cultures, which can lead to shorter diagnostics and prompt antibiotic treatment of these dangerous pathogens.
    Keywords Bacillus anthracis ; Francisella tularensis ; Yersinia pestis ; antibiotic resistance ; antibiotics ; blood ; diagnostic techniques ; humans ; morbidity ; mortality
    Language English
    Dates of publication 2021-0513
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9051055
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Evaluation of the European Committee on Antimicrobial Susceptibility Testing Guidelines for Rapid Antimicrobial Susceptibility Testing of

    Shifman, Ohad / Aminov, Tamar / Aftalion, Moshe / Gur, David / Cohen, Hila / Bar-David, Elad / Cohen, Ofer / Mamroud, Emanuelle / Levy, Haim / Aloni-Grinstein, Ronit / Steinberger-Levy, Ida / Rotem, Shahar

    Microorganisms

    2021  Volume 9, Issue 5

    Abstract: Rapid determination of bacterial antibiotic susceptibility is important for proper treatment of infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recently published guidelines for rapid antimicrobial susceptibility ... ...

    Abstract Rapid determination of bacterial antibiotic susceptibility is important for proper treatment of infections. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recently published guidelines for rapid antimicrobial susceptibility testing (RAST) performed directly from positive blood culture vials. These guidelines, however, were only published for a limited number of common pathogenic bacteria. In this study, we evaluated the applicability of these guidelines to three Tier 1 bioterror agents (
    Language English
    Publishing date 2021-05-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9051055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: A Rapid Antimicrobial Susceptibility Test for Determining

    Shifman, Ohad / Steinberger-Levy, Ida / Aloni-Grinstein, Ronit / Gur, David / Aftalion, Moshe / Ron, Izhar / Mamroud, Emanuelle / Ber, Raphael / Rotem, Shahar

    Frontiers in microbiology

    2019  Volume 10, Page(s) 754

    Abstract: Great efforts are being made to develop new rapid antibiotic susceptibility tests to meet the demand for clinical relevance versus disease progression. This is important especially in diseases caused by bacteria such ... ...

    Abstract Great efforts are being made to develop new rapid antibiotic susceptibility tests to meet the demand for clinical relevance versus disease progression. This is important especially in diseases caused by bacteria such as
    Language English
    Publishing date 2019-04-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2019.00754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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