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Background    Enterococcus faecium  and  faecalis  are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens.    Results  We extrapolate the transcriptomic data from a mice peritonitis infection model in  E .  faecalis  to identify putative up-regulated surface proteins under infection conditions in  E .  faecium . After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72%) between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaA fm, ) and the zinc ABC transporter substrate-binding lipoprotein (AdcA fm ). These candidate lipoproteins were overexpressed in  Escherichia coli  and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain  E .  faecium  E155 as well as clinical strains  E .  faecium  E1162,  Enterococcus faecalis  12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens.    Conclusion  Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier proteins together with polysaccharide antigens in vaccine development against enterococcal infections.

Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections