Brendel, Max
[Author]
;
Hammerschmidt, Sven
[Degree supervisor];
Fulde, Marcus
[Degree supervisor]Universität Greifswald
Charakterisierung der Enzyme für die Teichonsäureverankerung an der bakteriellen Zellwand und deren Einfluss auf die Pathophysiologie von Streptococcus pneumoniae
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Media type:
E-Book;
Thesis
Title:
Charakterisierung der Enzyme für die Teichonsäureverankerung an der bakteriellen Zellwand und deren Einfluss auf die Pathophysiologie von Streptococcus pneumoniae
Teichoic acids are among the most abundant cell wall polymers of Gram-positive bacteria. They are either anchored to the peptidoglycan and form wall teichoic acids, or they are anchored in the cell membrane via a glycolipid and thus form lipoteichoic acids. Unlike in other Gram-positive organisms, the biosynthesis and chemical structure of wall teichoic acids and lipoteichoic acids in S. pneumoniae is identical. Only the transfer of the teichoic acid chain to the peptidoglycan or the glycolipid anchor distinguishes the two glycopolymers from each other. In the present study, the influence of the LCP-proteins of S. pneumoniae on the physiology and pathophysiology of pneumococci was investigated. Using flow cytometry, field emission scanning electron microscopy and transmission electron microscopy, it was shown that the protein family has an influence on the amount of capsule content that can be produced and anchored by S. pneumoniae. Furthermore, various slight morphological changes of the different mutants could be detected, as well as restricted growth in complex and minimal medium for some of the lcp-mutants investigated. In the in vivo infection experiments, only minor differences were observed for the different mutants. The investigations of the phosphorylcholine content, with which the teichoic acids of S. pneumoniae are decorated, as well as the restricted growth behaviour, the increased susceptibility to various antibiotics and oxidative stress and the results of the in vivo experiments suggest that LytR and Psr are involved in the anchoring of the wall teichoic acids. However, further studies are necessary for a final clarification. In the second part of this work, it was shown that the loss of lipoteichoic acids leads to a serious change in membrane composition. An increased abundance of lipoproteins in the cell membrane was observed by flow cytometry, which led to a loss of membrane fluidity. This effect is dependent on the serotypes investigated and influences bacterial resistance to oxidative stress and antimicrobial peptides. Furthermore, limited adhesion to epithelial cells of the nasopharynx was demonstrated for strains without lipoteichoic acids. The observed changes lead to an attenuation of the lipoteichoic acid-deficient strains in the infection model of Galleria mellonella larvae and a reduced ability to colonise the murine nasopharynx.