Abstract
A substantial disease burden in vertebrates is due to Gram-negative bacteria that exclusively inhabit the upper respiratory or genitourinary tracts of their hosts and rely on directly acquiring iron from the host iron-binding glycoproteins through surface receptor proteins. The receptors enable these bacteria to proliferate independently from their neighbors on the mucosal surface and during invasive infection of the host. The diversity in these receptors evolved over millions of years of evolution, which thus bodes well for long-lasting vaccine coverage. Experiments in food production animals provide proof of concept for the use of engineered antigens derived from the receptor proteins to prevent colonization and invasive infection in the natural host, strongly supporting development of these vaccines for use in humans.