Studies on surface proteins of Gram-positive bacteria

Sammanfattning: Despite the availability of antibiotics and modern health care, infectious diseases continue to cause great suffering and costs. Bacterial surface proteins are important for the interaction between host and pathogen. This thesis gives an overview of the importance of bacterial surface proteins in Gram-positive bacteria, particularly Streptococcus pneumoniae and Streptococcus pyogenes. A novel contribution is the identification and characterization of a metal transport system in S. pyogenes, with broad specificity for trace metals. We have showed that this transporter, MtsABC, mediates bacterial acquisition of iron, zinc, and manganese. A MtsABC-deficient strain had attenuated virulence, and was highly susceptible to oxidative stress. We also observed reduced functionality of a manganese-dependent superoxide dismutase. Another contribution is the identification of a factor H-binding inhibitor of complement (Hic) in S. pneumoniae. This surface protein is encoded by the pspC locus, but homology between Hic and PspC is limited to the N-terminal part of the proteins. Hic binds fH with high affinity, and without interfering with the complement inhibitory effect of fH. FH is a major complement regulatory protein, and recruitment of fH to the bacterial surface may impair the activation of the alternative pathway. A bioinformatic work is also presented, where we develop and refine a pattern for computerized identification of cell wall-attached proteins (CWPs) in genomes from Gram-positive bacteria. Application of the pattern resulted in identification of 35 genes encoding putative CWPs, 19 of which were previously unknown.