Development of novel animal infection models for the study of acute and chronic Burkholderia pseudomallei pulmonary infections

Schaik, Erin J. van; Tom, Marina; DeVinney, Rebekah; Woods, Donald E.

doi:10.1016/j.micinf.2008.07.028

Cited by 19 publications

(26 citation statements)

References 23 publications

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“…4B). Lung histopathology clearly shows the formation of granulomas, which is similar to previously reported lung histopathology obtained for chronic B. pseudomallei lung infection (36). At 7 days postinfection, the rats were treated intranasally with itaconic acid; this treatment was repeated 2 days later with or without a concomitant intraperitoneal treatment with ceftazidime.…”

Section: Inhibition Of Icl Enzymatic Activity During Chronic B Pseudsupporting

confidence: 85%

“…The following plasmids were utilized in this study: pCR2.1-TOPO (Invitrogen), pBluescript SKII (Stratagene), pKAS46 (30), pTNS2, and pUC18Tmini-Tn7-Gm (3). , and 10 5 cells) of each B. pseudomallei parental, mutant, or complemented strain as previously described (36). Animals were monitored carefully for three consecutive days for signs of morbidity and mortality.…”

Section: Methodsmentioning

confidence: 99%

“…Four groups of eight rats per group were used for the chronic infection experiments. All animals in each group were inoculated intratracheally with 10 3 B. pseudomallei strain 1026b cells encased in agar beads as previously described (36). The rats in one group remained untreated.…”

Section: Methodsmentioning

confidence: 99%

“…This misdiagnosis has serious repercussions, as the treatments for B. pseudomallei and Mycobacterium tuberculosis infections are very different (10,26). In addition to these clinical similarities, we have described significant similarities between the pathological changes associated with tuberculosis and those seen in a chronic melioidosis animal model that we have developed, which include multiple-granuloma formation (36). Besides the similar lung pathology, both B. pseudomallei and M. tuberculosis infections can enter into a dormant phase, where there are no signs of infection (8,24).…”

mentioning

confidence: 89%

“…M. tuberculosis produces two distinct ICL enzymes, ICL-1 and ICL-2, that are jointly required for growth in vivo (21). Having demonstrated that B. pseudomallei is an intracellular pathogen that causes lung pathology similar to that caused by tuberculosis (36), we wished to determine if fatty acid metabolism is required for persistent B. pseudomallei infections.…”

mentioning

confidence: 99%

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Burkholderia pseudomalleiIsocitrate Lyase Is a Persistence Factor in Pulmonary Melioidosis: Implications for the Development of Isocitrate Lyase Inhibitors as Novel Antimicrobials

2009

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Burkholderia pseudomallei, the causative agent of melioidosis, has often been called the great "mimicker," and clinical disease due to this organism may include acute, chronic, and latent pulmonary infections. Interestingly, chronic pulmonary melioidosis is often mistaken for tuberculosis, and this can have significant consequences, as the treatments for these two infections are radically different. The recurrent misdiagnosis of melioidosis for tuberculosis has caused many to speculate that these two bacterial pathogens use similar pathways to produce latent infections. Here we show that isocitrate lyase is a persistence factor for B. pseudomallei, and inhibiting the activity of this enzyme during experimental chronic B. pseudomallei lung infection forces the infection into an acute state, which can then be treated with antibiotics. We found that if antibiotics are not provided in combination with isocitrate lyase inhibitors, the resulting B. pseudomallei infection overwhelms the host, resulting in death. These results suggest that the inhibition of isocitrate lyase activity does not necessarily attenuate virulence as previously observed for Mycobacterium tuberculosis infections but does force the bacteria into a replicating state where antibiotics are effective. Therefore, isocitrate lyase inhibitors could be developed for chronic B. pseudomallei infections but only for use in combination with effective antibiotics.

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Section: Inhibition Of Icl Enzymatic Activity During Chronic B Pseudsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 89%

mentioning

confidence: 99%

See 3 more Smart Citations

Burkholderia pseudomalleiIsocitrate Lyase Is a Persistence Factor in Pulmonary Melioidosis: Implications for the Development of Isocitrate Lyase Inhibitors as Novel Antimicrobials

2009

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History of the Early Biodetection Development

2014

Integrated Analytical Systems

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Low-Dose Exposure of C57BL/6 Mice to Burkholderia pseudomallei Mimics Chronic Human Melioidosis

Conejero

Patel

Reynal

et al. 2011

The American Journal of Pathology

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Burkholderia pseudomallei is the etiological agent of human melioidosis, a disease with a broad spectrum of clinical manifestations ranging from fatal septicemia to chronic localized infection or asymptomatic latent infection. Most clinical and immunological studies to date have focused on the acute disease process; however, little is known about pathology and immune response in chronic melioidosis. Here, we have developed a murine model of chronic disease by challenging C57BL/6 mice intranasally with a low dose of B. pseudomallei and monitoring them up to 100 days postinfection. Bacterial burdens were heterogeneous in different animals at all time points, consistent with the spectrum of clinical severity observed in humans. Proinflammatory cytokines such as gamma interferon (IFN-␥), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-␣ (TNF-␣) were induced during chronic infection, and histopathological analysis showed features in common with human melioidosis. Interestingly, many of these features were similar to those induced by Mycobacterium tuberculosis in humans, such as development of a collagen cord that encapsulates the lesions, the presence of multinucleated giant cells, and granulomas with a caseous necrotic center, which may explain why chronic melioidosis is often misdiagnosed as tuberculosis. Our model now provides a relevant and practical tool to define the immunological features of chronic melioidosis and aid in the development of more effective treatment of this disease in humans.

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Development of novel animal infection models for the study of acute and chronic Burkholderia pseudomallei pulmonary infections

Cited by 19 publications

References 23 publications

Burkholderia pseudomalleiIsocitrate Lyase Is a Persistence Factor in Pulmonary Melioidosis: Implications for the Development of Isocitrate Lyase Inhibitors as Novel Antimicrobials

Burkholderia pseudomalleiIsocitrate Lyase Is a Persistence Factor in Pulmonary Melioidosis: Implications for the Development of Isocitrate Lyase Inhibitors as Novel Antimicrobials

History of the Early Biodetection Development

Low-Dose Exposure of C57BL/6 Mice to Burkholderia pseudomallei Mimics Chronic Human Melioidosis

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