Treatment of plague: promising alternatives to antibiotics. J Med Microbiol

Laboratory for Plague Microbiology, Department of Infectious Diseases, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Serpukhov District, Moscow Region, Russia.
Journal of Medical Microbiology (Impact Factor: 2.25). 12/2006; 55(Pt 11):1461-75. DOI: 10.1099/jmm.0.46697-0
Source: PubMed


Plague still poses a significant threat to human health, and interest has been renewed recently in the possible use of Yersinia pestis as a biological weapon by terrorists. The septicaemic and pneumonic forms are always lethal if untreated. Attempts to treat this deadly disease date back to the era of global pandemics, when various methods were explored. The successful isolation of the plague pathogen led to the beginning of more scientific approaches to the treatment and cure of plague. This subsequently led to specific antibiotic prophylaxis and therapy for Y. pestis. The use of antibiotics such as tetracycline and streptomycin for the treatment of plague has been embraced by the World Health Organization Expert Committee on Plague as the 'gold standard' treatment. However, concerns regarding the development of antibiotic-resistant Y. pestis strains have led to the exploration of alternatives to antibiotics. Several investigators have looked into the use of alternatives, such as immunotherapy, non-pathogen-specific immunomodulatory therapy, phage therapy, bacteriocin therapy, and treatment with inhibitors of virulence factors. The alternative therapies reported in this review should be further investigated by comprehensive studies of their clinical application for the treatment of plague.

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    • "Plague is a lethal disease known for its important role in history, mainly as the cause of the Black Death [1-3]. Due to the emergence of antibiotics [4], plague no longer poses the same threat to public health as it did in the past. However, the disease is still present in almost every continent [5] causing fatalities that, during the last two decades, have fluctuated between several hundred to several thousand deaths per year [6]. "
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    ABSTRACT: Plague is caused by Yersinia pestis, a bacterium that disseminates inside of the host at remarkably high rates. Plague bacilli disrupt normal immune responses in the host allowing for systematic spread that is fatal if left untreated. How Y. pestis disseminates from the site of infection to deeper tissues is unknown. Dissemination studies for plague are typically performed in mice by determining the bacterial burden in specific organs at various time points. To follow bacterial dissemination during plague infections in mice we tested the possibility of using bioluminescence imaging (BLI), an alternative non-invasive approach. Fully virulent Y. pestis was transformed with a plasmid containing the luxCDABE genes, making it able to produce light; this lux-expressing strain was used to infect mice by subcutaneous, intradermal or intranasal inoculation. We successfully obtained images from infected animals and were able to follow bacterial dissemination over time for each of the three different routes of inoculation. We also compared the radiance signal from animals infected with a wild type strain and a Δcaf1ΔpsaA mutant that we previously showed to be attenuated in colonization of the lymph node and systemic dissemination. Radiance signals from mice infected with the wild type strain were larger than values obtained from mice infected with the mutant strain (linear regression of normalized values, P < 0.05). We demonstrate that BLI is useful for monitoring dissemination from multiple inoculation sites, and for characterization of mutants with defects in colonization or dissemination.
    BMC Microbiology 07/2012; 12(1):147. DOI:10.1186/1471-2180-12-147 · 2.73 Impact Factor
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    • "One of the first indications of the potential of Y. pestis phage occurred in the 1920s when d’Herelle used Y. pestis phages as a therapy to treat four plague-infected patients.80 He injected phages directly into the buboes of the patients; all four patients recorded a two-degree drop in temperature, and subsequently recovered. "
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    ABSTRACT: Bacteriophages (phages) have been utilized for decades as a means for uniquely identifying their target bacteria. Due to their inherent natural specificity, ease of use, and straightforward production, phage possess a number of desirable attributes which makes them particularly suited as bacterial detectors. As a result, extensive research has been conducted into the development of phage, or phage-derived products to expedite the detection of human pathogens. However, very few phage-based diagnostics have transitioned from the research lab into a clinical diagnostic tool. Herein we review the phage-based platforms that are currently used for the detection of Mycobacterium tuberculosis, Yersinia pestis, Bacillus anthracis and Staphylococcus aureus in the clinical field. We briefly describe the disease, the current diagnostic options, and the role phage diagnostics play in identifying the cause of infection, and determining antibiotic susceptibility.
    Bacteriophage 04/2012; 2(2):105-283. DOI:10.4161/bact.19274
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    • "Animals were protected from pneumonic plague following vaccination with the Y. pestis F1 and V antigens [26, 27]. F1 is a 17 kDa protein that forms a capsule and may interfere with complement-mediated opsonisation [26, 28]. The 37 kDa V virulence factor is a component of the Type 3 secretion system known as the “Yop virulon.” "
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    ABSTRACT: The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter.
    01/2012; 2012(8):731604. DOI:10.1155/2012/731604
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