Novel findings to the function and mechanism of the major autolysin (Atl) in staphylococci and excretion of cytoplasmic proteins

DSpace Repository

Show simple item record

dc.contributor.advisor Götz, Friedrich (Prof. Dr.)
dc.contributor.author Nega, Mulugeta
dc.date.accessioned 2020-12-22T14:51:21Z
dc.date.available 2020-12-22T14:51:21Z
dc.date.issued 2020-12-22
dc.identifier.other 1744864683 de_DE
dc.identifier.uri http://hdl.handle.net/10900/110916
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1109165 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-52292
dc.description.abstract The staphylococcal peptidoglycan (PGN) is a major and essential component of the cell wall. It is a dynamic structure that undergoes constant cycles of polymerization and hydrolysis which is carried out by transglycosylases/peptidases and PGN hydrolases. The major autolysin, Atl, is the most predominant PGN hydrolase in staphylococci. Though its structure and function have been studied extensively, little is known about the activity and interplay of its domains AmiA and GlcA during cell division and separation. With this study, a highly resolved complex structure of the catalytic amidase domain of S. aureus Atl was elucidated and its molecular ligand interaction mechanism and natural substrate specificity was resolved. Investigating the deletion mutants of both AmiA and GlcA, as well as AtlA revealed that each of the enzymes plays a significant role in cell aggregation, proper septum formation and cell separation. Notably, loss of GlcA activity results in aberrant septum formation manifested by deformed and in part “kidney” like cell clusters. Despite a lowered peptidoglycan crosslinking, the atl, amiA und glcA mutants were 10,000 to 100,000 times more tolerant to oxacillin than the parent strain. For the first time, this work shows the activity of both AmiA and GlcA on their natural substrate, PGN. We found out that AmiA activity is specific to its host PGN while the naked glycan backbone is the natural substrate of GlcA. Our results revealed that the resolution of PGN during cell separation occurs in a defined order, in which AmiA first hydrolyzes the crosspeptides, followed by GlcA chewing back the naked glycan and releasing disaccharides. Additionally, we disproved the hitherto conclusion and showed that GlcA is not an endo- but an exo-beta-N-acetylglucosaminidase. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=en en
dc.subject.classification Staphylococcus de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.ddc 610 de_DE
dc.subject.other cell wall en
dc.subject.other cell separation en
dc.subject.other major autolysin en
dc.subject.other peptidoglycan en
dc.subject.other N-acetylmuramyl-L-alanine amidase en
dc.subject.other exo-β-N-acetylglucosaminidase en
dc.title Novel findings to the function and mechanism of the major autolysin (Atl) in staphylococci and excretion of cytoplasmic proteins en
dc.type Dissertation de_DE
dcterms.dateAccepted 2020-06-18
utue.publikation.fachbereich Biologie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE

Dateien:

This item appears in the following Collection(s)

Show simple item record