Expanding our understanding of the role of siderophores in host-pathogen interactions | New Voices in Infection Biology

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Talk abstract:

Pseudomonas aeruginosa is an opportunistic human pathogen rated as a “serious threat” by the US Centers for Disease Control and the World Health Organization. It is of particular concern to patients with ineffective immune systems, including the elderly, patients recovering from chemotherapy, and patients with cystic fibrosis. The rising prevalence of drug-resistant bacteria demands new therapeutic avenues for treating P. aeruginosa infections. One approach receiving increasing attention is to target virulence determinants, rather than bacterial growth, to reduce the pathogenesis of infection without driving resistance to treatment. One key virulence factor for P. aeruginosa is the major siderophore pyoverdine. It not only provides the bacterium with ferric iron, a nutrient necessary for growth, but also regulates the production of several secreted toxins and biofilm formation. Additionally, we recently demonstrated that pyoverdine is capable of disrupting host mitochondrial homeostasis in C. elegans and murine macrophages, even in the absence of live pathogen, resulting in cellular and organismal death. Taken together, these discoveries position pyoverdine as a valuable target. This approach is validated by several other observations, including a correlation between the level of pyoverdine production and virulence in C. elegans, mammalian cells, or mice, as well as the ability of several compounds that prevent pyoverdine biosynthesis or function to rescue hosts from infection.