The Histological Lesions of Experimental Glanders

Duval, Charles W.; White, Percival G.

doi:10.1084/jem.9.4.352

Cited by 18 publications

(19 citation statements)

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“…The character of histopathologic changes in the livers of hamsters from our study generally agree with previous reports, 11,12 which noted granulomatous le-sions in the liver to be small but numerous. In our study, despite finding histopathologic lesions in livers (Fig.…”

Section: Discussionsupporting

confidence: 92%

The Hamster Model of Intraperitoneal Burkholderia mallei (Glanders)

et al. 1999

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Abstract. Thirty-one female Syrian hamsters (Mesocricetus auratus) were inoculated intraperitoneally with a lethal dose of Burkholderia mallei (Budapest strain). Hamsters were killed postinoculation on days 0 through 6. Lesions were first noted in the spleens on postinoculation day 1, and in mediastinal and mesenteric lymph nodes, mediastinum, liver, and bone marrow on day 2. Lesions were present in the lung and submandibular lymph nodes on day 3, and in the brain on day 5. The characteristic histopathologic change was necrotizing pyogranulomatous inflammation, often with hemorrhage. Lesions indicative of impaired vascular perfusion, such as ischemia and infarction, were evident at the later time points. Pathologic changes generally increased in severity and distribution with time, and almost all tissues were ultimately affected. Our findings suggest that intraperitoneal bacteria were rapidly transported to mediastinal lymph nodes by transdiaphragmatic lymphatics and ultimately seeded other tissues hematogenously. The results of the study indicate that the Syrian hamster is a useful small animal model for glanders.

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Section: Discussionsupporting

confidence: 92%

The Hamster Model of Intraperitoneal Burkholderia mallei (Glanders)

et al. 1999

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“…7F). Collectively, these findings suggest that (20,23,31). Consistent with these observations, several recent studies have shown that B. mallei can survive and replicate in a variety of murine macrophage cell lines (11,42,62).…”

Section: Downloaded Fromsupporting

confidence: 81%

“…mallei and B. pseudomallei are known to cause MNGC formation both in vitro and in vivo (7,11,20,24,28,49). At present, the relevance of MNGCs with respect to virulence is unclear; however, it has been proposed that giant cells may provide these pathogens with an immune-privileged niche in which to survive and replicate within a host (7).…”

Section: Vol 78 2010 Interactions Of B Mallei T6s Mutants With Macmentioning

confidence: 99%

Burkholderia mallei Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages

Burtnick

DeShazer

Nair³

et al. 2010

Infect Immun

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Burkholderia mallei is a facultative intracellular pathogen that causes severe disease in animals and humans. Recent studies have shown that the cluster 1 type VI secretion system (T6SS-1) expressed by this organism is essential for survival in a hamster model of glanders. To better understand the role of T6SS-1 in the pathogenesis of disease, studies were initiated to examine the interactions of B. mallei tssE mutants with RAW 264.7 murine macrophages. Results obtained by utilizing modified gentamicin protection assays indicated that although the tssE mutants were able to survive within RAW 264.7 cells, significant growth defects were observed in comparison to controls. In addition, analysis of infected monolayers by differential interference contrast and fluorescence microscopy demonstrated that the tssE mutants lacked the ability to induce multinucleated giant cell formation. Via the use of fluorescence microscopy, tssE mutants were shown to undergo escape from lysosome-associated membrane protein 1-positive vacuoles. Curiously, however, following entry into the cytosol, the mutants exhibited actin polymerization defects resulting in inefficient intra-and intercellular spread characteristics. Importantly, all mutant phenotypes observed in this study could be restored by complementation. Based upon these findings, it appears that T6SS-1 plays a critical role in growth and actin-based motility following uptake of B. mallei by RAW 264.7 cells.

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“…Deletion of the T6SS apparatus components (including the hcp1 gene) resulted in B. mallei and B. pseudomallei mutants that exhibited significant impairment in intracellular growth, intracellu-lar spread, and multinucleated giant cell (MNGC) formation (21,22). MNGC formation is characteristic of B. mallei and B. pseudomallei infections and has been detected in eukaryotic cell culture as well as in animal models of infection (21,23,24). MNGCs are believed to be involved in the ability of these organisms to establish persistent infections by allowing intracellular spread and immune evasion (1,22,25).…”

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confidence: 99%

Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders

et al. 2016

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Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ⌬tonB ⌬hcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. Burkholderia mallei, the causative agent of glanders, is a Gramnegative, obligate mammalian pathogen. Glanders is primarily a disease of solipeds, with rare cases occurring among humans (1, 2). Naturally acquired human cases occur in areas of endemicity, particularly among those exposed to infected solipeds (2-4). Additionally, cases have been reported among laboratory workers (5, 6). The World Organization for Animal Health coordinates ongoing efforts toward worldwide eradication; however, regional endemicity still exists in Africa, Asia, the Middle East, and South America (2). Recent equid outbreaks in the Middle East and Asia (7-9) set the stage for possible glanders reintroduction into disease-free regions; as a result, glanders has been classified as a reemerging disease.Glanders is a debilitating and often fatal disease transmitted via cutaneous and respiratory routes. Disease course and severity are route dependent, with respiratory cases being the most severe (3). Respiratory infection is characterized by rapid onset of symptoms, including fever, lymphadenopathy, pulmonary abscesses, pneumonia, disseminated organ infection, and, ultimately, septicemia (3, 5, 10). Because of the high incidence of septicemia following respiratory infection, fatality rates in human respiratory cases have been estimated at 90% without treatment and 40% with aggressive antibiotic therapy (11).The use of B. mallei as a biothreat agent has been documented in different world military conflicts (10,12,13). Its amenability to aerosolization, low infectious dose, high case fatality rate, and high-level antibiotic resistance make B. mallei a top candidate for malevolent use (1, 10). Because of its perceived public health threat, the Department of Health and Human Services has categorized B. mallei as a tier 1 select agent. The lack of effective treatments against these bacteria highlights the need for an effective vaccine. Numerous vaccine strategies have been tested; however, to date there are n...

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The Histological Lesions of Experimental Glanders

Cited by 18 publications

References 0 publications

The Hamster Model of Intraperitoneal Burkholderia mallei (Glanders)

The Hamster Model of Intraperitoneal Burkholderia mallei (Glanders)

Burkholderia mallei Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages

Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders

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