Abstract
BackgroundBurkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. We recently showed that NADPH oxidase but not nitric oxide (NO) contributes to resistance in innately resistant C57BL/6 mice in a B. pseudomallei respiratory infection model. However, the function of NO for resistance was shown to differ among distinct strains of mice and proved also to be stage dependent in various infection models. The present study therefore aimed to examine the role of NO in a systemic infection model of melioidosis and to test whether the function of NO differs among innately resistant C57BL/6 and susceptible BALB/c mice after B. pseudomallei infection.ResultsC57BL/6 iNOS-/- mice that were intravenously infected with B. pseudomallei survived several weeks, whereas most of the wild type animals succumbed during this period. The bacterial burden in liver and spleen was significantly higher in wild type animals compared to iNOS-/- mice 13 days after challenge. In contrast, BALB/c mice that were treated with amminoguanidine to inhibit NO expression in vivo showed significantly enhanced mortality rates and higher bacterial loads in liver and spleen compared to control animals. The bactericidal function of IFN-γ stimulated C57BL/6 iNOS-/- macrophages were not altered after B. pseudomallei infection, but BALB/c macrophages exhibited reduced killing activity against the pathogen when NO was inhibited.ConclusionOur present data indicate a dual role of NO among resistant and susceptible mouse strains after B. pseudomallei infection. NO mediated mechanisms are an essential component to control the infection in susceptible BALB/c mice. In contrast, NO production in B. pseudomallei infected C57BL/6 mice rather harmed the host likely due to its detrimental effects.
Highlights
Burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas
Whereas NADPH oxidase was crucial for resistance in C57BL/6 mice, we did not find any role for Nitric oxide (NO) to control B. pseudomallei infection in the resistant mouse strain in a respiratory infection model
To test whether NO might have a protective role after systemic infection with B. pseudomallei, we investigated iNOS-/- mice in an intravenous infection model of melioidosis
Summary
Burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. The function of NO for resistance was shown to differ among distinct strains of mice and proved to be stage dependent in various infection models. The present study aimed to examine the role of NO in a systemic infection model of melioidosis and to test whether the function of NO differs among innately resistant C57BL/6 and susceptible BALB/c mice after B. pseudomallei infection. A rather protective or damaging function for NO was Burkholderia pseudomallei comprises a facultative intracellular gram-negative rod and is the causative agent of melioidosis, an emerging infectious disease of humans and animals in certain areas of the tropics and subtropics [10]. Clinical manifestations are variable, ranging from inapparent to localized chronic infections and fulminant acute septicemias with high mortality rate [12]
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