Molecular determinants of sialic acid transport in pathogenic and commensal bacteria

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Sialic acids are amino sugar acids that are found in large numbers in human tissue. There, they play an important role in a variety of biological processes, such as communication between cells, cell adhesion and -recognition. However, sialic acids are also an important source of energy and carbon for probiotic or commensal bacteria such as Bacteroides fragilis or Akkermansia muciniphila. At the same time, sialic acid in human tissue is also exploited by pathogens such as Haemophilus influenzae by incorporating the molecule into the lipopolysaccharides of their cell wall, making the bacteria harder to recognize by the human immune system. Both pathogenic and commensal bacteria use special transporters to take up sialic acid from human tissue. Commonly used are so-called TRAP (tripartite ATP-independent periplasmatic) transporters or MFS (major facilitator superfamily) transporters. The structural and functional investigation of these transporters is therefore of high interest. Therefore, the aim of this proposal is to investigate the mechanism of sialic acid TRAP and MFS transporters. Ideally, structures in different intermediate steps of the transport cycle will be determined by cryo-electron microscopy. At the same time, the transport process will be followed by single-molecule fluorescence microscopy through the use of special, conformation-selective probes. By combining these structural and functional data, deep insights into the function of bacterial sialic acid transporters shall be obtained.