Chlamydia pneumoniae is a human respiratory pathogen that causes acute and chronic respiratory tract infections in humans. Cumulative evidence also has suggested that C. pneumoniae is a risk factor for cardiovascular disease and contributes to the pathogenesis of atherosclerosis, a disease of chronic inflammation. Hallmarks of chronic/persistent chlamydial infection are inflammation, fibrosis and scarring and chronic/persistent infections are difficult to treat. Persistent chlamydial infections in vitro are defined as the presence of the organism in a non-cultivable, but viable state, and can be induced by various factors such as cytokines, nutritional deprivation and various antibiotics. Persistence results from the arrest of the chlamydial developmental cycle in which the metabolically active, non-infectious form (the reticulate body) does not reorganize into the infectious elementary body. An important question is whether persistence occurs in human chlamydial infection and stimulates immunopathologic responses. Evidence of persistent Chlamydia infection in humans exists based on detection of chlamydial antigen/DNA in specimens from which the organism cannot be cultured and by antibiotic treatment failure. However, there are no clear diagnostic markers of persistent infection detecting viable organisms. C. pneumoniae antigen/DNA is detected frequently in atherosclerotic lesions, within foam cells, which are lipid laden vascular cells. Importantly, in mouse models of hyperlipidemia, C. pneumoniae infection accelerates atherosclerotic lesion progression; antimicrobial treatment has no effect, and evidence of the organism remains. The overall goal of this proposal is to determine if hyperlipidemia promotes persistence of viable C. pneumoniae organisms in the blood vessel, which are refractory to antibiotic treatment. These studies may identify diagnostic markers of persistent infection and provide insight into the lack of beneficial effects of antibiotc treatment in clinical trials on secondary prevention of cardiovascular disease.
Chlamydia pneumoniae is a human respiratory pathogen that has been associated with cardiovascular disease and thought to establish persistent infection of lipid laden vascular cells. The proposed studies will investigate whether hyperlipidemia induces persistence, a state in which the organism is uncultivable, but viable, and renders the organism resistant to antibiotics. These studies may identify diagnostic markers of persistent infection and provide insight into the absence of any beneficial effect of antibiotics in clinical trials on secondary prevention of coronary heart disease.
