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Enterococcus faecium is evolving as a multi-resistant pathogen causing infections with high morbidity and mortality. A protective vaccine against E. faecium is lacking up till now. ATP-binding cassette (ABC) transporter proteins have important functions in bacteria to maintain survival and homeostasis. In the present study, we evaluated the basic membrane protein (BMP) family ABC transporter substrate-binding protein, designated herein as BMP, as a potential vaccine candidate against E. faecium. Recombinant BMP of E. faecium was expressed in Escherichia coli, and purified by metal affinity chromatography. Swiss albino mice were immunized with the recombinant BMP combined with Bacillus Calmette–Guérin (BCG) and/or alum as adjuvants. Mice immunized with BMP combined with alternating BCG and alum developed BMP-specific IgG and were protected against E. faecium challenge as evidenced from organ bioburden and histopathological examination. Furthermore, serum from immunized mice showed enhanced opsonophagocytic activity and protected mice against E. faecium challenge by passive immunization. Bioinformatic analysis revealed appreciable degrees of homology between E. faecium BMP and proteins from other pathogens which suggests BMP could be a useful vaccine against multiple pathogens. To our knowledge, this is the first report of in-vivo evaluation of BMP as a potential vaccine candidate against E. faecium. [ABSTRACT FROM AUTHOR]