PLoS Pathog. 14, e1007102 (2018)

Pathogens such as Enterococcus faecalis require manganese (Mn) for growth and virulence, but the host can restrict the Mn levels available to the bacteria using metal-binding proteins such as calprotectin. To determine how E. faecalis is able to acquire Mn for growth, Colomer-Winter et al. performed genomic profiling using known streptococci Mn transporter sequences and identified three potential E. faecalis Mn transporters: EfaCBA (an ABC-type transporter), MntH1 and MntH2 (Nramp-type transporters). Testing the virulence of a panel of single-, double- and triple-deletion mutant strains, their ability to grow in Mn-restricted media and their susceptibility to inhibition by calprotectin, the authors determined that EfaCBA and MntH2 are the primary Mn transporters required for virulence in two different mammalian systems. Quantification of cellular Mn content of the mutants showed that all three transporters could effectively transport Mn and that the growth defect of the triple mutant is primarily due to its inability to acquire Mn. EfaCBA and MntH2 could also each support E. faecalis growth and biofilm formation in Mn-limiting conditions such as human serum or urine. These results reveal a new strategy by which E. faecalis is able to overcome the nutritional immunity imposed by mammalian hosts.