Nitric oxide determines the development of actinomycetoma byNocardia brasiliensisin eNOS knockout C57BL/6 mice

Abstract

Mycetoma is a chronic human infectious disease that produces severe deformation frequently in the lower extremities. Etiological agents include fungi (eumycetoma) and bacteria (actinomycetoma) that produce similar clinical and microscopic changes. The clinical appearance includes swelling, abscesses, ulcers, scars, and sinuses that drain purulent material with microbe microcolonies. The pathogenesis of actinomycetoma has been studied mainly in rodents. Using this approach, it was found that Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A. Nitric oxide (NO) is a molecule with biological activities depending on its local concentration. Its effect on killing intracellular bacteria such as Mycobacterium tuberculosis has been known for decades. NO plays an important role in innate and adaptive immunity. It can promote or suppress some biological activities despite its short half-ife. NO is produced by three different nitric oxide synthases (NOS). We used the genetic blockade of eNOS in C57BL/6 mice to demonstrate the role of NO in actinomycetoma development. Inflammation and actinomycetoma were prevented in genetically modified mice infected with Nocardia brasiliensis. T cell proliferation was increased in these rodents, and antibody production, IL-6, and IL-10 expression were similar and TNF-α was lower.

Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae

“…Bacterial flagella are potent antigens that are recognized by host TLR5 receptors to rapidly activate innate immunity and produce proinflammatory cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), which cause bacterial DNA damage and cell death [15][16][17][18]. V. cholerae has the ability to cope with host-produced ROS and RNS by upregulating OxyR-activated expression of dps, katG, prxA or AphB-mediated expression of ohrA in response to ROS [19][20][21] and NorR-mediated expression of nnrS and hmpA in response to RNS [22] or by promoting bacterial mutation frequency to improve environmental adaptability.…”