<i>In Vitro</i>
            Efficacy of Antibiotics Commonly Used To Treat Human Plague against Intracellular
            <i>Yersinia pestis</i>

Wendte, Jered M.; Ponnusamy, Duraisamy; Reiber, Deanna; Blair, Jeffrey L.; Clinkenbeard, Kenneth D.

doi:10.1128/aac.01481-10

Cited by 19 publications

(16 citation statements)

References 29 publications

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“…A cough develops with sputum production, which may be bloody, and increasing chest pain and difficulty in breathing. Pneumonic plague is invariably fatal unless antibiotic therapy commences within 24 h of the development of clinical symptoms [18]. …”

Section: Plaguementioning

confidence: 99%

Plague: Infections of Companion Animals and Opportunities for Intervention

Oyston

Williamson

2011

Animals

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Plague is a zoonotic disease, normally circulating in rodent populations, transmitted to humans most commonly through the bite of an infected flea vector. Secondary infection of the lungs results in generation of infectious aerosols, which pose a significant hazard to close contacts. In enzootic areas, plague infections have been reported in owners and veterinarians who come into contact with infected pets. Dogs are relatively resistant, but can import infected fleas into the home. Cats are acutely susceptible, and can present a direct hazard to health. Reducing roaming and hunting behaviours, combined with flea control measures go some way to reducing the risk to humans. Various vaccine formulations have been developed which may be suitable to protect companion animals from contracting plague, and thus preventing onward transmission to man. Since transmission has resulted in a number of fatal cases of plague, the vaccination of domestic animals such as cats would seem a low cost strategy for reducing the risk of infection by this serious disease in enzootic regions.

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Section: Plaguementioning

confidence: 99%

Plague: Infections of Companion Animals and Opportunities for Intervention

Oyston

Williamson

2011

Animals

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“…The infected macrophages were incubated at 37°C with 5% CO 2 for 45 min followed by 1 h of treatment with 10 μg/ml gentamicin for MH-S cells and 100 μg/ml gentamicin for RAW 264.7 cells to kill extracellular bacteria. The dose of the antibiotic used was empirically determined based on the host cell sensitivity, and an effective bactericidal range of gentamicin is from 7.5–200 μg/ml [59, 60]. The surviving bacteria inside the macrophages were enumerated immediately after the gentamicin treatment (0 h time point) and subsequently at 4h or at 8 to 24 h by serial dilution and plating on SBA plates [27, 36].…”

Section: Methodsmentioning

confidence: 99%

Further characterization of a highly attenuated Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease in murine alveolar and primary human macrophages

Lier

Tiner

Chauhan

et al. 2015

Microbial Pathogenesis

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We recently characterized the Δlpp Δpla double in-frame deletion mutant of Yersinia pestis CO92 molecularly, biologically, and immunologically. While Braun lipoprotein (Lpp) activates toll-like receptor-2 to initiate an inflammatory cascade, plasminogen activator (Pla) protease facilitates bacterial dissemination in the host. The Δlpp Δpla double mutant was highly attenuated in evoking bubonic and pneumonic plague, was rapidly cleared from mouse organs, and generated humoral and cell-mediated immune responses to provide subsequent protection to mice against a lethal challenge dose of wild-type (WT) CO92. Here, we further characterized the Δlpp Δpla double mutant in two murine macrophage cell lines as well as in primary human monocyte-derived macrophages to gauge its potential as a live-attenuated vaccine candidate. We first demonstrated that the Δpla single and the Δlpp Δpla double mutant were unable to survive efficiently in murine and human macrophages, unlike WT CO92. We observed that the levels of Pla and its associated protease activity were not affected in the Δlpp single mutant, and, likewise, deletion of the pla gene from WT CO92 did not alter Lpp levels. Further, our study revealed that both Lpp and Pla contributed to the intracellular survival of WT CO92 via different mechanisms. Importantly, the ability of the Δlpp Δpla double mutant to be phagocytized by macrophages, to stimulate production of tumor necrosis factor-α and interleukin-6, and to activate the nitric oxide killing pathways of the host cells remained unaltered when compared to the WT CO92-infected macrophages. Finally, macrophages infected with either the WT CO92 or the Δlpp Δpla double mutant were equally efficient in their uptake of zymosan particles as determined by flow cytometric analysis. Overall, our data indicated that although the Δlpp Δpla double mutant of Y. pestis CO92 was highly attenuated, it retained the ability to elicit innate and subsequent acquired immune responses in the host similar to that of WT CO92, which are highly desirable in a live-attenuated vaccine candidate.

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“…Doxycycline has been proposed as the drug of choice for post exposure prophylaxis in the case of a community contact with pneumonic plague [9].…”

Section: Post Exposure Prophylaxismentioning

confidence: 99%

Yersinia pestis: Plague

Laudisoit¹,

Ruppitsch²,

Stoeger³

et al. 2012

BSL3 and BSL4 Agents

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OrganismLaboratory category Transmissible by aerosol Yersinia pestis BSL-3 Yes Recommended Respiratory ProtectionRespiratory protection is highly advisable to provide respiratory protection against droplet transmission. A filtering facepiece (FFP3) mask or a positively ventilated mask attached to a FFP3 filter is recommended to avoid an infection via respiratory route. Similarly, eye protection is advisable. Recommended Personal Protective EquipmentAs for other BSL-3 pathogens, a laboratory coat, surgical gown (open-backed), with high collar, cuffed sleeves, closing on high-sleeved gloves together with double laboratory gloves should be used. The laboratory gown and gloves should always be changed when moving between laboratory areas. Best Disinfection Surface and EquipmentY. pestis is fragile and does not survive for long periods outside a host. It is readily destroyed by desiccation or by the action of common disinfectants, namely sodium hypochlorite 1%, ethanol 70%, glutaraldehyde 2%, iodine-based agents, and germicidal solutions that contain phenol, formaldehyde, and quaternary ammonium compounds [1]. Y. pestis is susceptible to inactivation by sunlight, by moist heat (121 • C for at least 15 min), or dry heat (160-170 • C for at least 1 h).

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In Vitro Efficacy of Antibiotics Commonly Used To Treat Human Plague against Intracellular Yersinia pestis

Cited by 19 publications

References 29 publications

Plague: Infections of Companion Animals and Opportunities for Intervention

Plague: Infections of Companion Animals and Opportunities for Intervention

Further characterization of a highly attenuated Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease in murine alveolar and primary human macrophages

Yersinia pestis: Plague

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