Lactoferrin-induced reduction of vanB vancomycin resistance in enterococci

The mucosal protein lactoferrin (LF) reduces the MIC of vancomycin for staphylococcal isolates sensitive to this glycopeptide. The purpose of this research was to investigate the effect of LF on the MIC of vancomycin for vanB resistant isolates of Enterococcus faecalis (Efs1) and E. faecium (Efm1). At a concentration of 2048 μg/ml, LF reduced the MIC of vancomycin 16-fold for Efs1 and eight-fold for Efm1. The cell wall precursors of Efs1 were examined following growth in media supplemented with LF, d-alanine or d-lactate. The precursors were extracted from harvested cells by ether and ion exchange chromatography and the amino acid and lactate composition was determined. Compared with that of unsupplemented media, d-alanine or LF supplementation caused an increase in the d-alanine content of the precursors. Concomitantly, the d-lactate content was reduced. Exogenous d-lactate did not affect the composition of the precursors. This suggests that LF caused an increase in the pool of pentapeptide cell wall precursors. The LF-induced reduction in the vancomycin resistance of enterococci at in vivo concentrations suggests a potential use for this protein as an adjunctive agent to vancomycin.