Publications by authors named "Ohad Shifman"

Bloodstream infections (BSI) are defined by the presence of viable bacteria or fungi, accompanied by systemic signs of infection. Choosing empirical therapy based solely on patient risk factors and prior antibiotic susceptibility test (AST) may lead to either ineffective treatment or unnecessarily broad-spectrum antibiotic exposure. In general, Clinical & Laboratory Standards Institute guideline-approved ASTs have a turnaround time of 48-72 h from sample to answer, a period that may result in a critical delay in the appropriate selection of therapy.

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The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension.

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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.

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The current monkeypox virus global spread and lack of data regarding clinical specimens' infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.

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As of July 2022, more than 16,000 laboratory-confirmed monkeypox (MPX) cases have been reported worldwide. Until recently, MPX was a rare viral disease seldom detected outside Africa. MPX virus (MPXV) belongs to the Orthopoxvirus (OPV) genus and is a genetically close relative of the Variola virus (the causative agent of smallpox).

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There is an urgent need for rapid antibiotic susceptibility tests to improve clinical treatment and to support antibiotic stewardship, especially concerning the emergence of multi-drug-resistant bacteria. Nowadays this need is even more profound due to progress in synthetic biology procedures that may facilitate the malicious preparation of engineered antibiotic-resistant pathogens. We recently described a novel, rapid, simple, specific, and sensitive method named a Micro-Agar-PCR-test (MAPt) and showed its performance on clinical as well as environmental samples.

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Objective: As part of a research aiming at the isolation of bacteria secreting growth inhibiting compounds, cultures of Francisella tularensis were implanted in environmental samples and monitored for inhibition zones on agar. Two antibiotic-like secreting bacteria were isolated, their genomic sequence was deciphered and taxonomic profiling analysis classified them as belonging to the Pantoea genus.

Data Description: Two bacterial isolates exhibiting growth inhibition zones to F.

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Rapid antibiotic susceptibility tests, performed directly on whole blood samples, will offer great clinical advantages. This issue is of considerable importance when it comes to bioterror pathogens where prompt antibiotic treatment should be offered to infected patients as well as prophylaxis to suspected exposed individuals. Herein, we describe a novel and rapid method, named MAPt, that is based on the direct application of a blood sample onto solid agar that has been embedded with different concentrations of the tested antibiotic.

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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.

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Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2) infection since the virus does not bind effectively to the murine version of the angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2-refractive CD-1 mice susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low doses of the acute lung injury stimulants bleomycin or ricin caused severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates greater than 50%.

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SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, emerged as the cause of a global crisis. Rapid and reliable clinical diagnosis is essential for effectively controlling transmission. The gold standard assay for SARS-CoV-2 identification is the highly sensitive real-time quantitative polymerase chain reaction (RT-qPCR); however, this assay depends on specialized reagents and may suffer from false results.

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We report the genome sequences and the identification of genetic variations in eight clinical samples of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Samples were collected from nasopharyngeal swabs of symptomatic and asymptomatic individuals from five care homes for elderly and infirm persons in Israel. The sequences obtained are valuable, as they carry a newly reported nonsynonymous substitution located within the nucleoprotein open reading frame.

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The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we show the development of a replication competent recombinant VSV-∆G-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2.

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Antibiotic resistance of bio-threat agents holds major concerns especially in light of advances in methods for engineering pathogens with antibiotic resistance. Preparedness means for rapid identification and prompt proper medical treatment are of need to contain the event and prevent morbidity and spreading of the disease by properly treating exposed individuals before symptoms appearance. Herein, we describe a novel, rapid, simple, specific, and sensitive method named Micro-Agar-PCR-test (MAPt), which determines antibiotic susceptibility of bio-terror pathogens, directly from environmental samples, with no need for any prior isolation, quantification, or enrichment steps.

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Article Synopsis
  • - The largest monkeypox outbreak in West Africa began in Nigeria in September 2017, leading to the first human cases being reported outside Africa when four travelers brought the virus to the UK, Israel, and Singapore.
  • - An analysis of epidemiological and molecular data revealed that the strains found in the travelers and a Nigerian case shared a recent common ancestor, indicating a possible single source of infection within certain Nigerian states.
  • - Findings suggest that the low genetic variation among the exported cases hints at a small, related group of monkeypox isolates as the source, potentially linked to genetic diversity in the monkeypox strains circulating in Bayelsa, Delta, and Rivers states.
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High-throughput DNA sequencing (HTS) of pathogens in whole blood samples is hampered by the high host/pathogen nucleic acids ratio. We describe a novel and rapid bacterial enrichment procedure whose implementation is exemplified in simulated bacteremic human blood samples. The procedure involves depletion of the host DNA, rapid HTS and bioinformatic analyses.

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We announce the genome sequences of two strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated in Israel, one imported by a traveler who returned from Japan and the second strain collected from a patient infected by a traveler returning from Italy. The sequences obtained are valuable as early manifestations for future follow-up of the local spread of the virus in Israel.

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Ricin, a highly lethal plant-derived toxin, is a potential biological threat agent due to its high availability, ease of production and the lack of approved medical countermeasures for post-exposure treatment. To date, no specific ricin receptors were identified. Here we show for the first time, that the low density lipoprotein receptor-related protein-1 (LRP1) is a major target molecule for binding of ricin.

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We report the whole-genome sequence of a monkeypox virus strain isolated in Israel. The strain was isolated in 2018 from a patient travelling back from West Africa. The virus was fully sequenced on the Illumina MiSeq and Oxford Nanopore Technologies MinION platforms.

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We report here the whole-genome sequence of the first camelpox virus case diagnosed in Israel. The strain (Negev2016) was isolated in 2016 from a camel in southern Israel and was sequenced on the Illumina MiSeq and Oxford Nanopore MinION platforms.

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In the event of a bioterror attack, a prompt, sensitive and definite identification of the agents involved is of major concern for confirmation of the event and for mitigation of countermeasures. Whether the information from intelligence forces is limited concerning the biothreat identity or one suspects the presence of a novel or engineered agent, the genetic identification of microorganisms in an unknown sample is challenging. High-throughput sequencing (HTS) technologies can sequence a heterogeneous mixture of genetic materials with high sensitivity and speed; nevertheless, despite the enormous advantages of HTS, all previous reports have analyzed unknown samples in a timeframe of a few days to a few weeks.

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We report here the draft genome sequence of MAA2018. This highly virulent strain was isolated in 2018 from the first melioidosis case in Israel associated with recreational travel to Goa, India.

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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 , the causative agent of plague, which grows rapidly but relatively slow . This compromises the ability to use standard growth-based susceptibility tests to obtain rapid and proper antibiotic treatment guidance.

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We report a case of monkeypox in a man who returned from Nigeria to Israel in 2018. Virus was detected in pustule swabs by transmission electron microscopy and PCR and confirmed by immunofluorescence assay, tissue culture, and ELISA. The West Africa monkeypox outbreak calls for increased awareness by public health authorities worldwide.

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