Different pathogens share similar medical settings and rely on similar virulence strategies to cause
infections. We have previously applied 3-D computational modeling and bioinformatics to discover novel
antigens that target more than one human pathogen. Active and passive immunization with the recombinant N-terminus of Candida albicans Hyr1 (rHyr1p-N) protect mice against lethal
candidemia. Here we determine that Hyr1p shares homology with
cell surface proteins of the multidrug resistant Gram negative bacterium, Acinetobacter baumannii including
hemagglutinin (FhaB) and
outer membrane protein A (OmpA). The A. baumannii OmpA binds to C. albicans Hyr1p, leading to a mixed species biofilm. Deletion of HYR1, or blocking of Hyr1p using polyclonal
antibodies, significantly reduce A. baumannii binding to C. albicans hyphae. Furthermore, active vaccination with rHyr1p-N or passive immunization with polyclonal
antibodies raised against specific
peptide motifs of rHyr1p-N markedly improve survival of diabetic or neutropenic mice infected with A. baumannii
bacteremia or
pneumonia. Antibody raised against one particular
peptide of the rHyr1p-N sequence (
peptide 5) confers majority of the protection through blocking A. baumannii invasion of host cells and inducing death of the bacterium by a putative
iron starvation mechanism. Anti-Hyr1
peptide 5
antibodies also mitigate A. baumannii /C. albicans mixed biofilm formation in vitro. Consistent with our bioinformatic analysis and structural modeling of Hyr1p, anti-Hyr1p
peptide 5
antibodies bound to A. baumannii FhaB, OmpA, and an outer membrane
siderophore binding protein. Our studies highlight the concept of cross-kingdom
vaccine protection against high priority human pathogens such as A. baumannii and C. albicans that share similar ecological niches in immunocompromised patients.