Monoclonal IgM antibodies raised againstCandida albicansHyr1 provide cross-kingdom protection against Gram negative bacteria

AbstractRecent years have seen an unprecedented rise in the incidence of multidrug resistant (MDR) Gram negative bacteria (GNB) such asAcinetobacterandKlebsiellaspecies. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent and treat infections by GNB are urgently needed. Previously, we have reported that theC. albicanshyphal-regulated protein Hyr1 shares striking 3D structural homology with cell surface proteins ofA. baumannii; and active or passive vaccination with rHyr1p-N or anti-Hyr1p polyclonal antibody, respectively; protect mice fromAcinetobacterinfections. Here, we show that monoclonal antibodies (mAb) generated against Hyr1p, bind to the surface ofAcinetobacteras well asK. pneumoniae. The anti-Hyr1 mAb also block damage to primary endothelial cells by the bacteria, and protect mice from lethal pulmonary infections mediated byA. baumanniiandK. pneumoniae. Our current studies emphasize the potential of harnessing Hyr1p mAb as a cross-kingdom immunotherapeutic strategy against MDR GNB.