الفهرس 
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Abstract
Multi-drug resistant (MDR) gram-negative bacteria (GNB) such as Acinetobacter baumannii (AB) and Klebsiella pneumoniae (KP) are associated with high mortality rates. New methods to prevent or treat these infections are needed. Candida hyphae regulated cell surface protein (Hyr1p) is predicted to share structural and sequence homology with the hemagglutinin/hemolysin protein (FhaB) and siderophore-binding protein of GNB including AB and KP, respectively. Indeed, passive immunization using
8 different Hyr1p peptides as a target protects against A. baumannii infections in mice especially peptide no. 5. Thus, we attempted to develop protective monoclonal antibodies (mAbs) and test their efficacy against A. baumannii and K. pneumoniae in vitro and in vivo. We generated and characterized 4 clones of IgM mAbs (H1, H2, H3, and H4) targeting Hyr1p, all mAbs bound to K. pneumoniae (KPC-RM, KPC-8, KPC-6, and KP- QR) and A. baumannii (HUMC-1, HUMC-6, and HUMC12) clinical isolates. Two of the mAbs resulted in protecting A549 epithelial cells from K. pneumoniae- or A. baumannii- induced damage by ” ” ” ” " ~ " ” ” ” ”70% and 100%, respectively when compared to respective epithelial cell damage in the presence of an isotype-matching control IgM (p<0.0001). Finally, one of the mAbs (H3) caused 70% and 100% long-term survival of mice infected with lethal doses of K. pneumoniae or A. baumannii, respectively (p<0.05). H3 treatment also lowered the lungs bacterial burden when compared to mice treated with isotype-matching control IgM (p <0.05). In conclusion, we used Candida Hyr1p to generate cross-kingdom protective mAbs against MDR K. pneumoniae and A. baumannii. Our results warrant the further development of these mAbs as novel immunotherapeutics against MDR GNB.