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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (2019)
Increasingly, clinical infections are becoming recalcitrant or completely resistant to antibiotics treatment and multidrug resistance is rising alarmingly. Patients suffering from infections that used to be treated successfully by antibiotic regimens are running out of the treatment options. Bacteriophage (phage) therapy, long practiced in parts of Eastern Europe and the states of the former Soviet Union, is now being reevaluated as a treatment option complementary to and synergistic with antibiotic treatments. We discuss some current studies that have addressed synergistic killing activity between phages and antibiotics, the issues of treatment order and antibiotic class, and point to considerations that will have to be addressed by future studies. Overall, co-treatments with phages and antibiotics promise to extend the utility of antibiotics in current use. Nevertheless, a lot of work, both basic and clinical, remains to be done before such co-treatments become routine options in the hospital setting.
    Creative Commons 'BY-NC-ND' version 4.0 license
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2021)

    This work presents evidence that temperate and virulent viruses impact the ecology, evolution, and health state of their bacterial and eukaryotic hosts across ecosystems including the ocean, human gut, and urban environment.

    Temperate viruses can switch between a lysogenic and a lytic lifestyle. In the lytic cycle, phage lyse the host cell shortly after infection to release the progeny into the environment. In the lysogenic cycle, phage integrate into the bacterial genome to replicate with it during cell division. Here, it is shown how bacteriophage, viruses that infect bacteria, are key drivers of evolution in the marine environment and presents ongoing work on a mechanism that regulates prophage lysogenic-to-lytic the switch in the human gut.

    Part of this research was conducted amidst a global pandemic caused by a virulent virus; this inspired the assembly of a workflow that combines community building with molecular biology to identify environmental reservoirs of SARS-CoV-2 and other eukaryotic RNA viruses. Using these methods, SARS-CoV-2 RNA was detected on surfaces of the urban environment and the risk of infection by contact with contaminated fomites in San Diego County was predicted. The viral RNA community present on these surfaces was also characterized.

    Lastly, with the aim to uncover novel virus-derived systems where bacteria interact with their eukaryotic host, this thesis presents the identification of a new phage tail-like contractile injection system in Bacteroides, that was found prevalent in the gut of healthy adults.

      Cover page: VIRULENT AND TEMPERATE VIRUSES: THE 2 FACES OF EVIL
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2016)
      The Critical Assessment of protein Structure Prediction (CASP) experiment would not have been possible without the prediction targets provided by the experimental structural biology community. In this article, selected crystallographers providing targets for the CASP11 experiment discuss the functional and biological significance of the target proteins, highlight their most interesting structural features, and assess whether these features were correctly reproduced in the predictions submitted to CASP11. Proteins 2016; 84(Suppl 1):34-50. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
        Cover page: Some of the most interesting CASP11 targets through the eyes of their authors
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2020)
        Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.
          Cover page: Discovery of several thousand highly diverse circular DNA viruses
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2018)
          Volume 61, no. 10, e00954-17, 2017, https://doi.org/10.1128/AAC.00954-17. Materials and Methods, 2nd paragraph, 2nd sentence: “Phages provided by the Biological Defense Research Directorate (BDRD) of the Naval Medical Research Center (AB-Navy1, AB-Navy4, AB-Navy71, AB-Navy97, and AbTP31) were isolated from various environmental samples by using routine isolation techniques, as previously described (9)” should read “Phages provided by the Biological Defense Research Directorate (BDRD) of the Naval Medical Research Center (AB-Navy1, AB-Navy4, AB-Navy97, and AbTP31) were isolated from various environmental samples by using routine isolation techniques, as previously described (9), except for one phage (AB-Navy71, also known as phage vB_Ab-M-G7, DSM strain no. 25639), which was purchased from Liebniz Institute DSMZ (Germany).”
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2017)
            Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
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