Metal ion acquisition and homeostasis are essential for bacterial survival, growth and physiology. A family of metal ion, ABC-type import systems have been identified in Gram-positive bacteria, in which the solute-binding proteins are predicted to be membrane-anchored lipoproteins. The prediction that the MtsA protein of Streptococcus agalactiae A909 is a lipoprotein was confirmed. The expression of MtsA was co-ordinately regulated by the presence of both manganese and ferrous ions suggesting that MtsA may be involved in the uptake of both these ions. MtsA was shown to be expressed at levels of ferrous ions known to be present in amniotic fluid, a growth medium for S. agalactiae during neonatal infection.

Although Streptococcus agalactiae, the group B Streptococcus, is a leading cause of invasive neonatal disease worldwide the molecular basis of its virulence is still poorly understood. To investigate the role of lipoproteins in the physiology and interaction of this pathogen with host cells, we generated a mutant S. agalactiae strain (A909DLgt) deficient in the Lgt enzyme and thus unable to lipidate lipoprotein precursors (pro-lipoproteins). The loss of pro-lipoprotein lipidation did not affect the viability of S. agalactiae or its growth in several different media, including cationdepleted media. The processing of two well-characterized lipoproteins, but not a non-lipoprotein, was clearly shown to be aberrant in A909DLgt. The mutant strain was shown to be more sensitive to oxidative stress in vitro although the molecular basis of this increased sensitivity was not apparent. The inactivation of Lgt also resulted in changes to the bacterial cell envelope, as demonstrated by reduced retention of both the group B carbohydrate and the polysaccharide capsule and a statistically significant reduction (P50.0079) in A909DLgt adherence to human endothelial cells of fetal origin. These data confirm that failure to process lipoproteins correctly has pleiotropic effects that may be of significance to S. agalactiae colonization and pathogenesis.