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Chronic Bacterial Pathogens: Mechanisms of Persistence, Page 1 of 2
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Persistent bacterial infections such as brucellosis and typhoid fever are characterized by a long incubation period that leads to chronic, sometimes lifelong, debilitating disease with serious clinical manifestations ( 1 ). Therefore, chronic bacterial diseases have a significant impact on public health, due to the utilization of resources for long-term treatment of patients ( 2 ). Additionally, chronic infections affect the ability of the ill to provide for their families, resulting in a significant socioeconomic burden in affected countries ( 3 ).
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0020-2015Full text loading...
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0020-2015Microgranuloma formation in spleen of Brucella-infected mice. (A) Fully developed microgranuloma (black arrow) at 30 days postinfection. Granuloma is composed of epithelioid macrophages surrounded by lymphocytes. Hematoxylin and eosin stain, 400x magnification. (B) Immunolabeling of Brucella abortus within microgranulomas in spleen at 30 days postinfection. Note the presence of bacteria inside macrophages (black arrow). Immunohistochemistry, 400x magnification.
Microgranuloma formation in spleen of Brucella-infected mice. (A) Fully developed microgranuloma (black arrow) at 30 days postinfection. Granuloma is composed of epithelioid macrophages surrounded by lymphocytes. Hematoxylin and eosin stain, 400x magnification. (B) Immunolabeling of Brucella abortus within microgranulomas in spleen at 30 days postinfection. Note the presence of bacteria inside macrophages (black arrow). Immunohistochemistry, 400x magnification.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0020-2015Macrophage metabolism during Brucella infection. During the acute phase of Brucella abortus infection (left), interferon-γ (IFN-γ) is transiently produced, resulting in a predominance of classically activated macrophages (CAMs). In these cells, oxygen is consumed by NADPH oxidase (Phox) to generate superoxide radicals, and energy is produced by anaerobic glycolysis. Since anaerobic glycolysis yields only 2ATP, the cell has to consume more glucose to meet its energy needs. In contrast, during the chronic infection phase (right), IFN-γ is absent, but interleukin-4 (IL-4) and IL-13 signal via STAT6 to induce the alternatively activated macrophage (AAM) phenotype. Activation of STAT6 increases the expression and activation of peroxisome proliferator-activated receptor gamma (PPARγ), which in turn upregulates genes controlling β-oxidation, thereby shifting cellular physiology toward oxidative pathways. As a result, less glucose is consumed for cellular metabolism, and the intracellular glucose concentration increases. This glucose can be utilized by B. abortus for growth within infected macrophages.
Macrophage metabolism during Brucella infection. During the acute phase of Brucella abortus infection (left), interferon-γ (IFN-γ) is transiently produced, resulting in a predominance of classically activated macrophages (CAMs). In these cells, oxygen is consumed by NADPH oxidase (Phox) to generate superoxide radicals, and energy is produced by anaerobic glycolysis. Since anaerobic glycolysis yields only 2ATP, the cell has to consume more glucose to meet its energy needs. In contrast, during the chronic infection phase (right), IFN-γ is absent, but interleukin-4 (IL-4) and IL-13 signal via STAT6 to induce the alternatively activated macrophage (AAM) phenotype. Activation of STAT6 increases the expression and activation of peroxisome proliferator-activated receptor gamma (PPARγ), which in turn upregulates genes controlling β-oxidation, thereby shifting cellular physiology toward oxidative pathways. As a result, less glucose is consumed for cellular metabolism, and the intracellular glucose concentration increases. This glucose can be utilized by B. abortus for growth within infected macrophages.
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0020-2015Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0020-2015Strategies for persistence a
Virulence Mechanisms of Bacterial Pathogens, Fifth Edition
. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0020-2015