Manipulation of host angioneogenesis: A critical link for understanding the pathogenesis of invasive mold infections?

Despite progress over the last decade, opportunistic mold infections continue to be associated with high rates of morbidity and mortality in immunocompromised patients. Given the propensity of molds to invade blood vessels, vasculopathy may be a barrier to effective delivery of antifungal drugs to infected tissue. In a recent study (Ben-Ami R et al. Blood, 2009), we found that A. fumigatus suppresses endothelial cell migration, differentiation and capillary tube formation both in vitro and in an animal model system. This effect is mediated by secreted secondary metabolites such as gliotoxin. Herein, I discuss the potential implications of how invasive molds modulate host angiogenesis in experimental and clinical mold infections. Strategies that employ reversal of vasculopathy, neutralization of metabolites that inhibit endothelial function, exploration of pro-angiogenic factors as diagnostic or prognostic markers affected patients will likely be the focus of future studies. This complex, yet emerging field might add another level of knowledge and therapeutic choices in the management of these devastated infections.