Abstract
When infecting a human host, Corynebacterium diphtheriae and Corynebacterium ulcerans are able to impair macrophage maturation and induce cell death. However, the underlying molecular mechanisms are not well understood. As a framework for this project, a combination of fluorescence microscopy, cytotoxicity assays, live cell imaging, and fluorescence-activated cell sorting was applied to understand the pathogenicity of two Corynebacterium strains isolated from fatal cases of systemic infections. The results showed a clear cytotoxic effect of the bacteria. The observed survival of the pathogens in macrophages and, subsequent, necrotic lysis of cells may be mechanisms explaining dissemination of C. diphtheriae and C. ulcerans to distant organs in the body.
Highlights
From the 90 Corynebacterium species described in 2014, approximately 50 species were initially isolated from humans or human clinical material [1]
Human infections associated with C. ulcerans, which can often be ascribed to zoonotic transmission, appear to be rising in European countries and have outnumbered diphtheria cases caused by toxigenic C. diphtheriae [9,10,11,12]
Previous studies indicated a deleterious effect at multiplicities of infection (MOI) higher than 50 for C. ulcerans [12] and C. diphtheriae strains [20,21] on human macrophage-like cells
Summary
From the 90 Corynebacterium species described in 2014, approximately 50 species were initially isolated from humans or human clinical material [1]. The disease was never fully eradicated and to date a few thousand cases are still reported to the World Health Organization every year [5,6] Due to this persistence and an overall case-fatality rate of 5% to 10%, with higher death rates of up to 20% among patients younger than 5 years and in unprotected patients, C. diphtheriae is still present on the list of the most important global death-provoking pathogens [7]. Nowadays, this ignominious role is challenged by a taxonomically closely related emerging pathogen, Corynebacterium ulcerans, which was first described by Gilbert and Stewart, who isolated this bacterium from the throat of a patient with diphtheria-like symptoms [8]. Human infections associated with C. ulcerans, which can often be ascribed to zoonotic transmission, appear to be rising in European countries and have outnumbered diphtheria cases caused by toxigenic C. diphtheriae [9,10,11,12]
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